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Home , Diallyl disulfide, Dihydrocapsaicin, Eucalyptol, Evodiamine, GSK1016790A, Hyperforin

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Note: The letters ‘f’ and ‘t’ following the locators refers to ﬁgures and tables cited in the text.

A Acyl-lipid desaturas, 455 AA, see Arachidonic acid (AA) Adenophostin A, 71, 72t aa, see Amino acid (aa) Adenosine 5-diphosphoribose, 65, 789 AACOCF3, see Arachidonyl triﬂuoromethyl Adlea, 651 ketone (AACOCF3) ADP, 4t, 10, 155, 597, 598f, 599, 602, 669, α1A-adrenoceptor antagonist prazosin, 711t, 814–815, 890 553 ADPKD, see Autosomal dominant polycystic aa 723–928 fragment, 19 kidney disease (ADPKD) aa 839–873 fragment, 17, 19 ADPKD-causing mutations Aβ, see Amyloid β-peptide (Aβ) PKD1 ABC protein, see ATP-binding cassette protein L4224P, 17 (ABC transporter) R4227X, 17 Abeele, F. V., 715 TRPP2 Abbott Laboratories, 645 E837X, 17 ACA, see N-(p-amylcinnamoyl)anthranilic R742X, 17 acid (ACA) R807X, 17 Acetaldehyde, 68t, 69 R872X, 17 Acetic acid-induced nociceptive response, ADPR, see ADP-ribose (ADPR) 50 ADP-ribose (ADPR), 99, 112–113, 113f, Acetylcholine-secreting sympathetic neuron, 380–382, 464, 534–536, 535f, 179 537f, 538, 711t, 712–713, Acetylsalicylic acid, 49t, 55 717, 770, 784, 789, 816–820, Acrolein, 67t, 69, 867, 971–972 885 Acrosome reaction, 125, 130, 301, 325, β-Adrenergic agonists, 740 578, 881–882, 885, 888–889, α2 Adrenoreceptor, 49t, 55, 188 891–895 Adult polycystic kidney disease (ADPKD), Actinopterigy, 223 1023 Activation gate, 485–486 Aframomum daniellii (aframodial), 46t, 52 Leu681, amino acid residue, 485–486 Aframomum melegueta (Melegueta pepper), Tyr671, ion pathway, 486 45t, 51, 70 Acute myeloid leukaemia and myelodysplastic Agelenopsis aperta (American funnel web syndrome (AML/MDS), 949 spider), 48t, 54 Acylated phloroglucinol hyperforin, 71 Agonist-dependent vasorelaxation, 378 Acylation, 96 Ahern, G. P., 526–527 Acyl-homoserine lactone, 163, 836 Aiptasia pulchella (anemone), 54

M.S. Islam (ed.), Transient Receptor Potential Channels, Advances in Experimental 1033 Medicine and Biology 704, DOI 10.1007/978-94-007-0265-3, C Springer Science+Business Media B.V. 2011 1034 Index

Airway cells of non-neuronal origin, TRP Allicin (2-propenyl 2-propene thiosulfinate), channels in, 974 66 airway structural and immune cells, Allium, 66, 67t 975–976 Allosteric coupling, 517, 524, 527f, 528 capsaicin receptor and, 976–978 Allosteric gating in thermoTRP, 481–483 intracellular calcium homeostasis and allosteric MWC model, 481, 482f inflammation, 975 capsaicin gating of TRPV1, 481 TRPA1, 974–975 coupling of electric energy, 483 Airway chemoreceptor, 163 single channel recordings, 483 Airway irritation, 641 voltage gating, 483 Airway SMC, molecular expression and Allosteric gating scheme, 525–527 functional role Allyl isothiocyanate (AITC), 66, 67t, 69, 73, active NSCCs 110, 190t, 485, 766, 792, 852, cell-attached single channel recordings, 972 733 Alpha-amino-3-hydroxy-5-methyl-4- homomeric/heteromeric, 734 isoxazolepropionic acid multiple TRPC molecules (AMPA), 156, 161, 547, 576, guinea-pig airway SMCs, 732 999 human airway SMCs, 732 Al-Shawi laboratory, 29 porcine airway SM tissues, 732 ALS/PD, see Guamanian amyotrophic lateral TRPC3-encoded NSCCs sclerosis and parkinsonian 2+ agonist-induced increase in [Ca ]i, dementia (ALS/PD) 736–737 Alvarez, O., 469–486 expression and activity in asthmatic Alveolar capillary endothelium, 978 airway SMCs, 740–741 Alzheimer, 175, 382, 537–538, 575 mediated Ca2+ influx, 739 Alzheimer’s disease, 175, 382, 537 Na+/Ca2+ exchanger-1 and/or L-type Amantini, C., 947–961 Ca2+ channels, 737–738, 737f Ambudkar, I. S., 435–445, 547, 824 phospholipase C activation, 739 + AMG-517, 653–654 resting [Ca2 ]i lowered, 736 Amgen, 646, 652–653 Vm hyperpolarization, 734 TRPC3/TRPC6 gene silencing, 739 Amide I band, 458 Airway smooth muscle hyperreactivity, Amiloride, 278, 750, 839, 863t, 869–870, 920 797–798 Amino acid (aa), 2, 17, 19, 150, 230, AITC 419t–420t, 537f elicited control response vs. signal, 184, 536, 537f comparison, 110 218, 536 Ajoene, 66, 67t 538–557, 536, 537f Aka Mcoln2, see TRPML2 1292–1325, 536, 537f Akey,J.M.,259–260 2-Aminoethoxydiphenyl borate (2-APB), 56, Akt/PKB, 954–955 88, 89f, 91–93, 190, 420, 477, Alarm/defense mechanism, 197 711t, 735t, 852 Albatrellus confluens (neogri- 2-Aminoethyl diphenylborinate (2-APB), 627 folin/albaconol/grifolin), Amino (N) termini, 2f, 2, 3t, 8–9, 12, 15, 211, 47t, 52–53 316, 392, 415, 440, 463, 547, Albatrellus ovinus (scutigeral), 47t, 52 710, 719, 919, 930, 1011 Albert,A.P.,391–404 2-Aminophenylborate (2-APB), 176 ALG-2 protein, 215 4-Aminopyridine, 733 Alkylation, 96 Aminoquinazolines, 647 Allen, E., 921 Amoroso, S., 586 Allergic asthma, 973, 976 AMPA receptor, 156, 161, 547, 576, 999 Allicin (garlic), 66, 67t, 110, 115, 470, 623, Amplification mechanism, 317, 375 782, 792 AMP–PNP (an ATP analog), 10, 11f, 155 Index 1035

AMTB (TRPM8 blocker), 89f, 97, 193t, 195, 2-APB, see 2-Aminoethoxydiphenyl borate 711t, 716 (2-APB); 2-Aminoethyl Amyloid β-peptide (Aβ), 382, 534, 537 diphenylborinate (2-APB) Analgesia, 197–199, 201, 503, 622, 626, 629, 2-APB action, 91–93, 111f, 176, 177t, 190, 647 191t, 420, 441, 477, 584, 603, Analgesic polypeptide HC1 (APHC1), 48t, 54 627, 675, 711t, 715–716, 735t, Anandamide, 48t, 54–55, 61, 142, 190, 768, 932 191t, 493, 556, 646, 822, 893, APHC1, see Analgesic polypeptide HC1 914–915, 953, 989–990, 992, (APHC1) 997 Apical calcium channels, 934, 958 Anaphylaxis, 976 Apoptosis, 55, 177, 200, 215, 231t, 254, 256, Ancistrodial, 47t, 52 263, 279, 288, 294–295, 327, Ancistrotermes cavithorax (ancistrodial), 47t, 532, 536–537, 575, 579, 585, 52 669, 675, 789, 820, 851, 853, Androgen-dependent (AD), 933, 938–939 929–931, 935–938, 940, 948, Androgen-independent (AI), 200, 931, 933 950–956, 959–960, 977 Apoptotic-induced cell death, 947, 949 Androgen-insensitive neuroendocrine phenotype, 254 Apoptotic-resistant neuroendocrine phenotype, 254, 931 Androgen sensitivity, 199–200 Appaloosa horse phenotype, 140, 142, Andrographis paniculata (bitter herbaceous 1017–1018 plant), 61 AP180 protein, 226 Andrographis paniculata (Chinese herb), 627 Aquaporin, 5f, 6, 28, 282f Angiogenesis, 347–348, 708, 710, 711t, Arachidonic acid (AA), 48t, 58t, 61–62, 767–769, 772, 774t, 791, 63t, 64t, 65, 68t, 71, 72t, 94, 795–796, 891, 930, 948, 960 128, 188, 380, 395, 418, 532, Angiotensin (Ang) II receptor, 160, 179, 278, 578, 617, 627, 674–675, 739, 376, 400, 669, 691–692, 715, 763–764, 771, 774t, 792, 800, 719, 764, 787f, 789, 793f, 1013 816, 819, 822, 824, 835, 890, Anionic lysophosphatidylinositol, 65 893, 915–916, 956, 990 Ankyrine-rich TRP (TRPA), 12, 26, 43, 88, Arachidonic acid metabolites, 48t, 58t, 68t, 71, 289, 323, 326–327, 331, 342, 72t, 94, 617, 627, 774t, 890 363, 364t, 365, 365t, 367t, 416, 2-Arachidonoylglycerol, 61 457, 469, 474–475, 493, 547, Arachidonyl trifluoromethyl ketone 563, 616, 688, 710, 732, 750, (AACOCF3), 94 760, 782, 948, 974, 988, 1011 Araki, I., 861–871 Ankyrin repeat domain (ARD), 12, 14 A7R5 aortic smooth muscle cells, 563 X-ray crystallography, 12 A7r5 cells, see Aortic smooth muscle cells Ankyrin repeats, 8f, 12, 13f, 14, 27, 32, 34, (A7r5 cells) 244, 517, 623, 638f, 639, 1013t, ARD, see Ankyrin repeat domain (ARD) 1013, 1015t Arf6, see GTPase ADP-ribosylation Factor 6 Annexin A1, 11, 177–179, 233, 691, 784, 918 (Arf6) pathway Anterior hypothalamus, 998 Arg701, 643–644 Anti-aging factor, see Kallikrein Aromatase deficient (ArKO) mice, 248 Anti-androgen therapy, 199, 938 ARPE19 cell line, 234 Anti-anxiety drugs, 991 Arrhenius, 473 Antidepressant drugs, 991–994 Arrhenius activation energy, 473 Anti-estrogen-receptor (ER), 959 Arrhythmogenic alteration, 180 Anti-inflammatory assay, 55 Arteriosclerosis, 782 Antioxidant enzymes, 532 Arthritis, 458, 618, 640t Aortic smooth muscle cells (A7r5 cells), 563, Artmann, G., 461, 464 693–694, 783, 797, 800 A7r5 vascular smooth muscle cell, 90 Aortic stenosis, 786 Aryl cinnamides, 649t 1036 Index

Asakawa, M., 851 and PC-1 function, signalling pathway, Ashford, M. L., 811 290 Asian spice, see Zanthoxylum piperitum A8V, 261–262 (Szechuan pepper) Axonal growth cones, 576, 579 Asn604, 644 AZD-1386 (AstraZeneca), 652t, 654 Aspirin, 55 Asp964 residue, 381 B Asthma, 688, 691–692, 740–741, 973, BAA, see Bisandrographolide A (BAA) 976–977 Bacterial K+ channel (KcsA), 1, 6, 643 Astrocytes, 936, 952, 955, 957 Baez-Nieto, D., 469–486 A563T, 261–262 Bandell, M., 481 ATG initiation codon, 136 BAPTA-AM, 404 Atomic force microscopy, 14, 17 Barritt, G. J., 667–680 Atomic resolution, 6, 33–34 Basic fibroblast growth factor (bFGF), 557, ATP binding, 10, 12, 13f, 150f, 154–155, 157, 576–577, 988 261 Bates-Withers, C., 173–180 ATP-binding cassette protein (ABC Bax, 938, 960 transporter), 151, 157, 814 Bayliss, A., 798 + ATP-dependent K channel (KATP ), 158, 812 Bayliss effect, 158, 160, 798–799 ATP-evoked calcium signalling, 131 Bayliss, W., 158 ATP +Mg2+, 437 Bayliss, W. M., 694 ATP synthesis, 669 B-cell receptor (BCR), 375–376, 375f Atropine, 549t, 597, 599, 722 B-cell signaling, 375 Automated patch clamp Anno 2010 Bcl-2, 938–939, 950 results, 110–120 BCR, see B-cell receptor (BCR) HEK293-TRPA1 cell testing on QPatch, Beckwith–Wiedemann syndrome, 939 111f Bedouin, 1020–1021 TRPA1, 110–112 Beech, D. J., 114 Benign prostatic hyperplasia (BPH), 201 TRPCs, 112–115 Benzimidazol analogue, 649t TRPMs, 112–115 Berbey, C., 753 TRPVs, 115–118 Bernd Nilius, 463 See also individual entries Beta-cell, 94, 538–539, 558 Autophagic dysfunction, 210 Beta-galactoside-binding lectin Galectin 1 Autophagic vesicle, 235 (GAL1), 934, 958 Autophagocytosis, see Autophagy Bezzerides, V. J., 550 Autophagosome, see Autophagic vesicle bFGF, see Basic fibroblast growth factor Autophagy, 210, 211t, 215, 231t, 234, 367t (bFGF) Autosomal dominant polycystic kidney disease Bhave, G., 498 (ADPKD), 17, 71, 73, 88, Biaryl carboxamides, 647, 649t 289–290, 771, 919 Biliary epithelial cells (cholangiocytes), 298, arterial hypertension, 290 667 cardiac and vascular manifestations, 290, Bindels, R., 240, 279 290f Binshtok, A. M., 622 Cre-loxP recombination system (Bio) chemical process, 452, 454 deletion of Pkd1, 290 Bioinformatics, 62, 362, 367, 469, 471f cysts in Biological antioxidants “two hit” mechanism, 289 absorbic acid, 532 extra-renal cysts, 290 α-tocopherol, 532 fatal ESRD, 289 Biosynthetic menthol precursor, see Menthone PKD1 or PKD2 genes, 289 Bisandrographolide A (BAA), 61, 330, 627, TRPP2 822 family, 289 3,5-Bis(trifluoromethyl)pyrazole, 750 Index 1037

Bitter/gustducin/TRPM5 pathway, 61, 157, Broad-spectrum inhibitor, see N-(p- 163, 298, 784, 832, 833f, 834, amylcinnamoyl)anthranilic acid 836, 838f (ACA) BK channels, 524, 527, 799 Bronchoconstriction, 641 Bladder cancer cell, 200 Bronchodilators, 976 Bladder micturition reflex, 195 Brussels sprouts, 66 Blastocyst, 915 BSA, see Bovine serum albumin (BSA) Blaumuller C., 353 B. subtilis, 455 B-lymphocyte, 226, 375–376, 445, 949 BTP2, see N-[4-3,5-bis(trifluromethyl)pyrazol- B16 mouse melanoma cell line, 136 1-yl]-4-methyl-1,2,3- BNP, see Brain natriuretic peptides (BNP) thiadiazole-5-carboxamine Boels, K., 558 (BTP2) Boiling globule, 459 Budding Yeast Bollimuntha, S., 573–587 biochemical studies with purification, 34 Boltzmann distribution law, 473 cryo-EM structures, 30–33 Boltzmann equation, 518 electron cryo-microscopy/single Bone cancer, 618, 648t particle analysis, TRPV1 Borate compound, 93 structure, 31f Borneol-evoked response, 59 reported channel structures, Boswellia sp., 57t, 60 comparison, 33f Botulinum neurotoxin A, 556 TRPV1 structures, similarity, 32f Boulay, G., 547 divide and conquer approach, 33–34 Boustany, C., 678 functional studies and genetic screens, Bovine serum albumin (BSA), 644 34–35 Bovine testis, 129, 886 ion channel structural biology, 27–28 eukaryotic membrane proteins, 27 Bowman’s capsule, 278 Saccharomyces cerevisiae, expres- BPB, see p-bromophenacyl bromide (BPB) sion/functional analysis, BPH, see Benign prostatic hyperplasia (BPH) 28–30 Brachyolmia, 61, 73, 1014–1016 TRP channel family, 26–27 Brachyolmia, type 3, 1014–1015 cytoplasmic amino-terminal domain, 26 chromosome 12q24.1-q24.2, 1014 distribution/determination, significance, R616Q/V620I mutations in HEK, 27 expression of, 1014 heterologous expression studies, 35 SOX9 pathway, 1014–1015 TRPA (ankyrin), 26 TRPV4 gene, mutations in, 1014 TRPC (canonical), 26 Bradycardia, 641 TRPML (mucolipin), 26 Bradykinin (BK), 31, 109, 179, 198, 328, 436, TRPM (melastatin), 26 497, 504, 506–507, 524, 552, TRPP (polycystin), 26 597, 617, 624, 691, 715, 719, TRPV (vanilloid), 26 764, 790–791, 799, 852, 865, voltage-gated cation channel, relation, 887, 890, 894, 971–973 26 Brain, 537, 596, 988–990 Büldt, Dr. G., 461, 464 Brain-derived neurotrophic factor (BDNF), Bunker, L. E., 232 343, 576–577, 579, 583, 585, Buraei, Z., 19 988, 991 Burdyga, T., 707–723 Brain natriuretic peptides (BNP), 788 5-Butyl-7-chloro-6-hydroxybenzo[c]- Brain, TRP channels in quinolizinium chloride TRPC channels, 988–989 (MPB-104), 157 TRPV channels, 989–990 Brauchi, S., 477, 479–481, 517–528 C Brefeldin A, 553, 561 Ca2+-activated CAN current, 604 Brevetoxin, 54 Ca2+-activated NSCC (CAN) channels, 713, Brinkmeier, H., 749–756 814 1038 Index

Ca2+-bound calmodulin, 535 795, 799, 812, 814–816, 818, Ca2+-calmodulin (Ca2+-CaM), 12, 16, 378, 820–823, 821f, 887, 894, 910, 379f, 380 913, 931, 936–937, 939, 957 Ca2+/calmodulindependent kinase IV Calcium chelators (CaMKIV), 583, 989 BAPTA, 109 Ca2+/calmodulin inhibitors, 675 EGTA, 109 Ca2+/calmodulin phosphorylation, 754 Calcium homeostasis, 88, 295, 350, 559, 687, Ca2+-CaM, see Ca2+-calmodulin (Ca2+-CaM) 887, 918, 975 Caco-2 cell, 245–246 Calcium-permeable ion channels Cacospongia mollior (scalaradial), 46t, 52 non-voltage gated non-selective cation Ca2+-dependent cellular response, 374 channels (NSCC), 708 Ca2+-dependent inactivation (CDI), 245, 421, non-voltage gated NSCC, 708 + 423, 437, 440–441 voltage-gated Ca2 channels (VGCC), 708 Ca2+-desensitization, 154–155, 815 “Calcium-related gene spray,” 319 cADPR, see Cyclic adenosine diphosphoribose Calcium-release-activated current (ICRAC), (cADPR) 93, 157–158, 160, 414–415, Caenorhabditis elegans, 223, 360, 931 418, 421, 423, 424f, 437–438, Ca2+ entry-evoked translocation, 375 440–441, 443 Ca2+ entry mechanism, 88, 90, 92, 94, 98, 262, Calcium store depletion, 112, 715, 886 436 Calmodulin (CaM), 30, 34, 127, 151, 154, 178, 2+ 2+ 330, 377, 379, 417, 440, 444, [Ca ]i, see Intracellular Ca concentration 2+ 495, 500, 506, 535f, 558, 582, ([Ca ]i) Ca2+ induced Ca2+ release (CICR), 815–816 601, 605, 639, 675, 694, 713, Ca2+ inﬂux, 52, 55, 65, 96, 99, 128–129, 735t, 753–754, 793f, 885, 887, 161, 188, 244, 246, 253, 257, 889–890, 894, 918, 931 279, 374–378, 375f, 379f, Calmodulin (CaM)/IP3R-binding (CIRB) 382, 416–417, 436, 495, 496f, motif, 330 497–499, 501–502, 533, 535f, Calvert, C. M., 318 535–536, 538–539, 573–577, CaM, see Calmodulin (CaM) 579–586, 619, 625, 637, CaM dependent kinases (CaMK), 581 693–697, 709, 712–713, 717, CaM/IP3 receptor-binding (CIRB) domain, 721f, 737–740, 737f, 742, 127 750, 753–755, 763–765, 768, CaMK, see CaM dependent kinases (CaMK) 771–772, 774t, 786, 788, cAMP, see Cyclic adenosine monophosphate 791–795, 797, 799, 820, 833f, (cAMP) 867, 869–870, 886, 888–889, Camphor, 57t, 59, 62, 68t, 115, 330, 470, 485, 893, 935–936, 939, 952, 954, 627, 852–853 957, 959, 974–975, 977–978, Camphor (+)-borneol, 59 996, 1015, 1018 Cancer pain, 640t, 648t Calbindin-D28k, 244, 246, 257–258 Cannabinoids Calcineurin-NFAT signalling pathway, 376, 9-tetrahydrocannabinol (THC), 625 754 WIN55215, 625 Calcitonin gene related peptide (CGRP), 492, Cannabinol, 56, 57t, 68t, 69, 330 624, 627, 640, 651, 790, 856, Cannabis sativa 863–868, 999 CB1 antagonist, 53 2+ Calcium ([Ca ]i), 128–129, 153f, 154, 158, CB2 antagonist, 53 161–163, 279, 344, 378, 382, non-psychotropic constituents, 56 392, 401, 436, 439, 444–445, cannabidiol, 56 505, 532–533, 535f, 536–537, cannabinol, 56 539, 574, 576, 581, 585, 688, Canonical TRPs, 99, 416, 549, 573–587, 782, 695–697, 711t, 713, 715, 910, 988, 1012 719–722, 720f, 721f, 734–742, Capacitative Ca2+ entry, see Store-operated 735t, 760, 763–768, 771, 790, Ca2+ entry (SOCE) Index 1039

Ca2+ permeability, 153–154, 212, 643, 737, cysteine S-nitrosylation of TRPC5, 792 737f, 742 11,12-EETs, 792–793 + Ca2 -permeable channels, 29, 148, 153, 200, endothelial cell migration, 795 415–416, 578, 643, 669, 670f, icillin, 793 673, 691, 718, 760, 763–764 increases endothelial permeability, 791, Capers, 66 795 Capsaicin (CPS), 470, 539, 615–616, 914–915, MgL mice exhibit diminished eNOS 950, 970, 974, 977, 997–1000 expression, 793 receptor, 976–978 mouse model of hypomagnesemia, 793 -sensitive polymodal respiratory irritant permeability of pulmonary vascular sensor, 970–971 endothelium regulation, 792 Capsaicin-induced dermal vasodilation role in endothelium derived (CIDV), 653 vasodilatation, 792 Capsaicin injection to masseter muscle treatment with siRNA, 795 acute nocifensive responses, 618 TRPA1 identified in endothelial cells, masseter hypersensitivity development, 792 618 TRPC3 activity, inhibition, 792 Capsazepine, 50–51, 53, 55, 98, 115, 116f, 117, 117, 188, 191t, 197, 200, TRPC4 in TRPC4–/– mice, deletion, 539, 642, 647, 648t, 655, 674, 791 697–698, 711t, 823, 840f, 850, TRPC6 protein, translocation, 792, 793f 863t, 867, 977–978, 992–993, VEGF increases vascular permeability, 997 791 Capsicum, 43 heart, physiological function and capsaicin (8-Methyl-N-vanillyl-trans-6- pathophysiological implications nonenamide), 44 in adult mouse cardiomyocytes, 789 dihydrocapsaicin, 44 apoptosis, 789 Carbachol, 328, 548t, 550, 552–553, 555, arrhythmia, 786 598–603, 821f, 866, 931 cardiac arrhytmia, 790 Carboxamide cardiac hypertrophy, 786 derivatives cardiomyopathy, 786 CPS-113, 188 chest pain, 790 CPS-369, 188 dilated cardiomyopathy, 790 WS-12, 188 Duchenne muscular dystrophy (DMD), Carboxyl (C) termini, 2, 2f, 3t, 8–9, 15, 790 278, 316, 392, 400, 416, 421, hypertrophic factors, 786 440–441, 463, 547, 616, 639, 12-lipoxygenase-derived eicosanoids, 710, 784, 919, 1011, 1016, 1023 790 Carboxylic acid NO-cGMP-PKG pathway, 788 derivative PARP activation, 789 WS-30, 188 in rat neonatal cardiomyocytes, 787 Cardiac hypertrophy, 754, 782 arrhythmias, 162 sildenafil in mice, 788 delayed afterdepolarization, 162 tolloid-like 1 gene deletion, 789–790 early afterdepolarization, 162–163 TRPC3 channels, inhibited, 787 Cardiac remodeling, 180 TRPC1-deficient mouse model, 788 Cardiomyopathy, 376, 754, 756, 782, 786–787, TRPC1 in cardiac hypertrophy, 788 790 TRPC6 phosphorylation in mouse Cardiopulmonary vasculature hearts, 787f, 788 endothelial cells of systemic and pulmonary TRPM4 levels increased, 789 circulation SMC of systemic vasculature angiogenesis, 795 activated by α1-adrenergic agonists, cardiovascular benefits, 792 797 1040 Index

Cardiopulmonary vasculature (cont.) TRPP family alveolar hypoxia-mediated vaso- detected in umbilical vein endothelial constrictive phenomenon, cells, 785 798 in heart, 785 ATP-induced mitogenesis, 797 in human coronary arterial smooth Bayliss effect, 798 muscle cells, 785 blocked by suppressing TRPC6 TRPV channels expression, 797 activated by heat, 786 Ca2+ influx, 797 in bladder, 786 cell swelling, 799 in keratinocytes, 786 heteromeric TRPC1/5 complex, in kidney, 786 activation, 796 in smooth muscle cells, 786 + intracellular Ca2 and PKC activation, Cardiovascular system, 537, 699, 781–782 800 Ca2+ release-activated Ca2+ channel protein 1 + Mg2 influx, 799 (CRACM1), 92, 418 migration, 797 Ca2+ release activated Ca2+ (CRAC), 161, neointima formation, 796 177, 414–415, 418, 419t, 421, normotensiveWKY rats, 799 423, 425, 437–445, 673 PLA2 activated, 800 Ca2+ release-activated Ca2+-selective (CRAC) proliferation, 795–796 channels, 414–415, 934, 958 in rat pulmonary artery smooth muscle Carrageenan, 617–618, 627, 649t cells, 797 Carrageenan injection to gastrocnemius muscle regulation of myogenic tone, 798 mechanical hyperalgesia, 618 STIM1, down-regulation, 797 Carvacrol, 57t, 59, 65, 330, 627, 853, 956 synthetic phenotype, 796 Case-by-case basis, 460 TRPC1 activity and expression, 796 Ca2+ sensor, 92, 245, 415, 418, 423, 574f, 581, TRPC3 and TRPC6, up-regulation, 798 671t, 673–674, 824 TRPC6–/– mice and wild-type mice, Ca2+ signals, 92, 291, 295, 374–376, 378–379, comparison, 798 395, 414, 445, 717, 786 in TRPC6–/– mouse model, 797 Caspases, 950 TRPM4 antisense oligonucleotides in -3 activation, 952 living rats, 800 Castillo, J. P., 469–486 TRPA channels CaT1, see Ca2+ transport protein subtype 1 channel tetramerization, 782 (CaT1) intramolecular interactions, 782 Catalase, 532 membrane localization, 782 Catechol-O-methyltransferase (COMT), 994 TRPA1 activated, 782 Caterina, M. J., 480 TRPC channels Cathepsin B, 936, 955 calcium sensor STIM, 783 Ca2+ transportation DAG production, 783, 787f function, 244–245 detected in embryonic brain, 783 intestinal absorption, 243 Orai channels, 783 regulation, 244–245 TRPM family renal reabsorption, 243 ADP-ribose pyrophosphatase activity, transcellular pathways identification, 784 240–241 C-termini, 784 TRPV5, epithelia, 243–244 mice with genetically disrupted See also TRPV5, TRPV6 TRPM5, 784 Ca2+ transport protein subtype 1 (CaT1), 93, NUDT9 domain, 784 240, 917 pronounced voltage modulation, 784 Caveolin-1, 377–379, 549t, 560, 764, 792 TRPM4, 5 and 7 in cardiomyocytes, Caveolin 1-rich lipid rafts, 533 expression, 785 Cayouette, S., 547 TRPM6 gene in HSH, 785 CB1 receptor, 69, 990, 992, 997–998 Index 1041

CB2 receptor, 990, 998 calmodulin, 178 CCI, see Chronic constriction injury (CCI) calmodulin kinase II, 178 CCR, see Coiled coil character (CCR) calpain, 178 CD38, 380, 538 phosphoinositol 3-kinase, 178 cDNA fragment, 115 Cell proliferation, 88, 139, 178, 200, 256, 263, cDNA library, 44, 137, 240 381–382, 414, 436, 442, 534, C12E8, see Dodecyl octaethylene glycol ether 539, 558, 563, 576–577, 581, (C12E8) 669, 675, 678, 679f, 710, 768, C. elegans, 210, 213, 230–232, 240–241, 773f, 774t, 781, 794, 796–797, 293, 323–333, 361–363, 364t, 929, 932, 935, 937, 939, 948, 365t, 365, 547, 548t, 554, 556, 954, 956, 959–960, 988 562–566 Cellular magnesium homeostasis, 178 C. elegans, activation of TRP channels in, Centers (sites) of native aggregation, 461 323–333, 324f Central nervous system (CNS), 302, 492, 556, mechanical activation, 328–329 577, 584, 604–606, 618–620, mammalian TRP channels, 328 629, 639, 832, 861, 864f, mechano/osmo-sensation, 328–329 988–990, 997–1000 mechanosensitivity, 328 Cerebellar purkinje cells, 579, 584, 596, 990 TRPA-1, 329 Cerebellar purkinje neurone, 398, 576, TRP-4/TRPN1, 329 579–580 other activation modes, 329 Cerebral ataxia, 579 mammalian TRPA1, 329 thermo-TRPs, 329 Cerebral cortex, 44, 582, 584, 639 TRPM channels, 329 Cerny, A. C., 545–566 receptor-operated activation, 327–328 Cervical cancer cell, 935, 953 PIP2 hydrolysis, 328 CFA, see Complete Freund’s Adjuvant (CFA) TRPA-1, 328 CFA-induced radiant heat inﬂammatory TRPC channels, 328 hyperalgesia, 197 TRPV channels, 328 CFTR, see Cystic Fibrosis Transmembrane C. elegans TRP channels, 323–333, 324f Conductance Regulator (CFTR) activation of TRP channels in C. elegans CGRP, see Calcitonin gene related peptide mechanical activation, 328–329 (CGRP) other activation modes, 329 Cha, S. K., 561 receptor-operated activation, 327–328 Chahl, L. A., 987–1000 functions of TRP channels in C. elegans Changeux, J. P., 481 TRPA subfamily, 326–327 Chang, Q., 560 TRPC subfamily, 325 Channel gating process, 518–519 TRPML subfamily, 327 Channel recruitment, 436, 444, 507 TRPM subfamily, 326 Chanzyme (Channel – Enzyme), 112, 975 TRPN subfamily, 327 TRPM6 and TRPM7, 714 TRPP subfamily, 327 Chaperone TRPV subfamily, 325–326 expression proteins regulation of TRP channels in C. elegans TRPA subfamily, 331 DnaJ, 452 TRPC subfamily, 330 DnaK, 452 TRPML subfamily, 331–332 GrpE, 452 TRPM subfamily, 331 CHAPS, see 3-[(3-Cholamidopropyl)- TRPN subfamily, 331 dimethylammonio]-1-propane TRPP subfamily, 331–332 sulfonate (CHAPS) TRPV subfamily, 330–331 Charcot–Marie–Tooth disease type 2C Cell-cycle progression, calcium-dependent (CMT2C), 14, 26, 61 proteins Chelate chromatography, 30 calcineurin, 178 Chemical genetics, 464 1042 Index

Chemokine gene, 161, 187, 381, 381f, 382, oak ridge polycystic kidney (orpk) 618, 688, 717, 891, 949, 975, mouse, 291 977 Tg737 gene, 291 Chemokine MCP1, 977 features of primary cilium, 291 Chemokines (CCL2), 161, 187, 381, 381f, 382, 9 + 0 axoneme, 291 618, 688, 717, 891, 949, 975, eukaryotic cilia, 291 977 TRPP2 and PC-1, 291 Cheng, K. T., 426, 435–445, 824 Ciliated OSNs, 344 Chest tightness, 970 cyclic nucleotide-gated channel A2 subunit, CheY-P (response regulator protein), 457 344 Chicken (Gallus gallus), 350 olfactory marker protein (OMP), 344 Chinese hamster ovary (CHO) cell, 62, 65, 126, OR-type odorant receptors, 344 142, 151, 328–329, 557–558, 1,8-Cineole, 62 560, 564, 710, 795, 799 Cinnamaldehyde (cinnamon), 67t, 69, 110, Chironex ﬂeckeri (box jellyﬁsh), 54 111, 111f, 190, 192t, 623, 852 5-(4-Chloro-3-methylphenyl)-1-[(4- Cinnamomum camphora, 57t, 59, 68t methylphenyl)methyl]- Cinnamomum cassia, 67t, 69 N-[(1S, 2S, 4R)-1,3,3- Cinnamomum zeylanicum, 45t, 50, 67t, 69 trimethylbicyclo[2.2.1]hept-2- Cinnamosma fragrans (cinnamodial/ yl]-1H-pyrazole-3-carboxamide cinnamosmolide/cinnamolid), (SR144528), 191 46t, 52 Chlorothiazide (CTZ), 256, 258–259 CIRB, see CaM/IP3 receptor-binding (CIRB) CHO cell, see Chinese hamster ovary (CHO) domain cell Circular dichroism spectropolarimetry, 3-[(3-Cholamidopropyl)-dimethylammonio]- 173–174 1-propane sulfonate (CHAPS), Circumferential stretch, 772 6 Citral Cholinergic blockers, 740 fragrant component, 59 Chromosome 2, 186 citronella, 59 Chromosome 7, 136, 150 lemongrass oil, 59 lemon peel, 59 Chromosome 19, 150, 210, 297 palmarosa grass, 59 Chromosome III, 210 isomeric mixture, 59 Chromosome 3L, 210 geranial, 59 Chronic constriction injury (CCI), 197–198, terpenoids neral, 59 626 Citrate, 627 Chronic hypertension, 786 Citric acid cycle, 669 Chronic hypoxia-induced PAH (CH-PAH), 696 Citrobacter rodentium-induced transmissible Chronic obstructive pulmonary disease murine colonic hyperplasia (COPD), 73, 772, 774t, 970, model, 254 976, 978 Civamide Cream, 651 Chronic persistent cough, 640t Civamide Nasal Solution, 651 Chronic respiratory diseases, 970 c-Jun N-terminal kinase (JNK), 178, 960 Chuang, H. H., 480 Clapham, D., 576 Chu, X., 127 Clapham, D. E., 173–180, 576, 581 Chung, G., 629 Classic or canonical TRP (TRPC), 88, 99, 493 Chung, M. K., 93, 484, 615–629, 640 Clathirin-coated endocytosis, 226 Chymotrypsin, 552 Claudius’ cell, 230 Cilia (primary) and polycystic kidney disease, CL4 cell line, 233–234 291–292 CLC7 (lysosomal Cl− channel), 213 cyst formation, 291 Clogging, 213 defects in primary cilium Clotrimazole, 88, 89f, 94–95, 95f, 190, 192t, chlamydomonas reinhardtii, 291 711t, 716 Index 1043

Clotrimazole, 1-[(2-Chlorophenyl) Conopeptide analogue, see Noxious diphenylmethyl]-1H-imidazole, mechanosensation blocker-1 94 (NMB-1) Cloudman, A. M., 232 Constitutively active (CA) channels, 329, 392, CMC, see Critical micelle concentration 709, 715, 733 (CMC) Core body temperature (CBT), 648t, 653–654 CMD (CRAC modulatory domain), 419t, 421, Cornell, R. A., 341–352 440 Corpuscles of Stannius, 352 CMT2C, see Charcot–Marie–Tooth disease Correa, A. M., 474 type 2C (CMT2C) COS-1 cell, 28 CNR1and CNR2 gene, 998 COS-7 cell, 6, 551, 558, 890 Cochlear hair cells, 234, 627 COS-M6 cell, 126 Coda, 486 Cough, 73, 509, 640t, 641, 652t, 653, 970–972 pore dilation processes, 486 CPA, see Cyclopiazonic acid (CPA) CPS, 935, 950–952, 952f, 954, 960 sine qua non feature of thermoTRP CRAC, see Ca2+ release activated Ca2+ channels, 486 (CRAC) Coiled coil character (CCR), 534, 537f Cre recombinase expressing mice, TRPV5 Coiled–coiled region, 26 promoter driven Coiled-coil folding motif, 463 generation, 283–284 Cold allodynia, 197–198, 624, 626 of DCT2 and CNT, 283 Cold and menthol receptor, 714, 973–974 map of pBS185 plasmid, 284f Cold hyperalgesia, 197–198, 624, 628 MAR and NarI/SpeI restriction sites, Cold-shock protein (CSP), 452 284 Cole-Moore effect, 528 SpeI and XhoI restriction sites, 284, Colletti, G. A., 209–217 284f Colquhoun, D., 162 validation and breeding, 284 Colsoul, B., 815–816 DCT2/CNT-specific AQP2 knockout Complete Freund’s Adjuvant (CFA), 197–198, mice and control mice, 284 504, 617–618, 625–626, TRPV5-Cre or MAR-TRPV5- Cre mice 648t–650t with floxed AQP2 mice, 284 Complex kidney function, 242 Critical micelle concentration (CMC), 6 Concavalin A, 534 Crotonaldehyde, 67t, 69 Conformational coupling, 294, 436 Croton tiglium, 58t, 61 Conformational entropy, 460 Crouzin, N., 586 cryo-EM, see Electron cryo-microscopy Congenital stationary night blindness (CSNB), (cryo-EM) 140–141, 1017–1020 CSNB, see Congenital stationary night in Appaloosa horses, 1017–1018 blindness (CSNB) in Caucasian non-consanguineous family, CSP, see Cold-shock protein (CSP) 1018 C-terminal His12, 29 chromosome 15q, homozygosity on, 1018 C-terminal (TRPM2-TE), 534, 536, 537f homozygous mutations C-terminus, 534 allelic heterogeneity in CSNB1B, gating kinetics, 186 1018–1019, 1019t PIP2 modulation, 186 deletion of exons (Y72-K365del), 1018 temperature sensitivity, 186 missense mutation (R14W), 1018 CTZ, see Chlorothiazide (CTZ) truncation mutation (W856X), 1018 Cup-5 gene, 210 in humans, 1018 Curcumin, 45t, 51 screening, 1018 Current-voltage (I–V) relationship, 137, 152f, Connecting tubule (CNT), 240, 243, 245, 247, 176, 187, 196, 317, 712, 763, 259, 278–279, 281–285, 282f, 817 284f Cutaneous A- and C-fiber terminals, 627 1044 Index

CXCL2, 381 DCT2, see Distal convoluted tubule (DCT2) CXCL8, 381, 381f DDM, see N-dodecyl-β-D-maltoside (DDM) Cyanea capillata (lion’s mane jellyfish), 54 Decavanadate, 65, 155, 157, 711t, 716 Cyanobacterium Synecocystis, 454 Dekermendjian, K., 637–656 Cyclic adenosine diphosphoribose (cADPR), Dekker, N., 637–656 380, 534, 538, 711t, 713, 816, Delmas, P., 294 818–819 Denda, M., 847–856 Cyclic adenosine monophosphate (cAMP), Dendreon, 188, 200 246, 497–498, 557–558, 628, Dendritic cell, 160, 931, 976 643, 711t, 824, 882, 893 Dendritic filopodia, 576 Cyclic AMP-response-element binding protein Dendritic microvilli, 127 (CREB), 579, 583, 797, 989 De novo synthesis, 65 Cyclic terpene alcohol, see Menthol Dental and orofacial pain, 622 Cyclin D1, 179 Dental pain, 621, 652t, 653–654 12,14 Cyclooxygenase inhibitor, see Ibuprofen 15-Deoxy- -prostaglandin J2 (15d-PGJ2), Cyclooxygenase reaction, 55, 93, 792, 850 68, 70, 623 Cyclopiazonic acid (CPA), 90, 393, 403–404, Depression and anxiety, 990–994 601, 693, 696, 739, 783 TRPC channels, 991–992 Cymbopogon (hydroxy-citronellal), 62, 64t TRPV channels, 992–994 CYP, see Cytochrome P450 (CYP) D-erythro-sphingosine, 65, 820 Cys553, 377 Desensitization, 50, 54–55, 59–60, 97, Cys558, 377 154–155, 187–188, 495–503, Cysteines 508–509, 539, 552, 556, 615, Cys-929, 186 625–626, 643–644, 655, 815, Cys-940, 186 834–835, 973, 992, 997–998 Cysteine S-nitrosylation, 377 DeSimone, J. A., 839 Cyst formation in mammals/zebrafish, DesK protein, 455 348–349 DesR protein, 455 polycystin-2 (PC2), 348 Destabilizing configurational entropy, 460 trpp2 MO-injected zebrafish embryos, 348 Detergents, use zebrafish trpp2 mutants, 348 crystallization, 6 Cystic Fibrosis Transmembrane Conductance purification, 6 Regulator (CFTR), 45t, 150f, solublization, 6 157 Ggen, 460 Cystitis, 640t, 870, 952 Gion, 460 Cytochrome P450 3A enzyme, 95 DGK, see Diacylglycerol kinase (DGK) Cytochrome P450 (CYP), 771 D333G mutation, 14, 1015t, 1016 Cytochrome P450 enzyme reaction, 93 Gother, 460 Cytokine gene, 157, 161, 187, 381, 381f, 618, Gtr, 460 669, 688, 759, 766, 789, 796, DHN, see Dorsal horn neurons (DHN) 912, 949, 975–977 DHPG Cytokine TNF-α, 618, 976 activator of PKC, 602 2+ Cytosolic Ca concentration, 296, 392, 414, activator of “plateau” depolarization, 602 760, 956 amplitude of depolarization, reduced, 602 Cytrochrome P 450-3A4, 50 application of PdBU, 602 Diabetic neuropathy, 621 D Diabetic painful neuropathy, 642t DADS, see Diallyl disulfide (DADS) Diacylglycerol (DAG), 43, 91f, 99, 126, 163, DAG, see Diacylglycerol (DAG) 188, 374, 533, 553, 619, 783 DAS, see Diallyl sulfide (DAS) activated channel, 397–400 DATS, see Diallyl trisulfide (DATS) IP3,role,398 Davies,A.J.,629 PIP2, direct vs. indirect actions, Cp, see Heat capacity change (Cp) 399–400 Index 1045

and PIP2 interactions, 398–399 Dot-blot analysis and RT-PCR studies, role, 397–398 305–306 biochemical cascade, 398 Dougherty, G., 303 Ca2+ open channel block, 396 3-D particle, 31 excitatory and inhibitory effects, 398 DPBA, 627 12,14 gated channel, 401–402 15d-PGJ2, see 15-Deoxy- -prostaglandin TRPC4 and TRPC5 channel activation, J2 (15d-PGJ2) PIP2 role, 401 Dragicevic, C., 469–486 generation and metabolism pathways, 396f DRG, see Dorsal root ganglia (DRG) physiological coupling, 400 Drosophila, 90, 230 PIP , inhibitory action, 400 TRP, 98 2 γ TRP and TRPL channel gating, pivotal TRP , 90, 99 generation, 396 TRPL, 90, 99 non-PLC-mediated pathways, 398 Drosophila melanogaster, 108, 112, 361, 367t TRPC3-C7 homomer, 397 Drosophila phototransduction, 547 TRPC4 and TRPC5 Drosophila S2 (Schneider) cell, 221, 225, 415, 438 exogenous OAG inhibition, 401 Drosophila trp mutant, 26 PKC activity inhibition, 402 Drost-Hansen, W., 454 Diacylglycerol kinase (DGK), 128 Drug discovery cascade, machine 2,4-Diacylphloroglucinol derivative (Hyp9), implementation 89f, 97 assay optimization, 108 Diallyl disulfide (DADS), 66, 67t cardiac liability, 108 Diallyl sulfide (DAS), 66, 67t lead optimization, 108 Diallyl trisulfide (DATS), 66, 67t secondary screening, 108 Dictyostelium, 230, 316 DT40 B lymphocyte, 96, 374–375, 377 Dietrich, A., 781–800 DT-40 cell, 178, 374, 438, 539, 785, 886–887 Diffusible messenger, 436 Ducret, T., 687–699 Digel, I., 451–464, 822 Dulac, C., 129 1,25-Dihydroxycholecalciferol, 562 Duncan,L.M.,937 Diphtheria toxin A fragment (DTA), 837 Dunker, A. K., 459 Disrupted bipolar transmission, 140 Dye ruthenium red, 69, 99, 110, 111f, 246, Disrupted in schizophrenia 1 (DISC1), 994 251, 484, 643, 647, 695, 711t, Distal (early/late) convoluted tubules 715, 771, 792, 794, 797, 848, (DCT1/DCT2), 243, 247, 259, 852, 854, 918, 978 278, 561, 563 Dynamin-dependent endocytotic pathway, 565 1,3-Disubstituted urea derivatives, 648t Dynamin (Dyn1aK44A), 226, 549t, 559 Diterpenoid incensole acetate, 60 Dysbindin, 994 Divalent cations, 88, 153, 175, 178, 187, 244, Dysfunctional mitochondria, 210 330, 642 Dyspnea air hunger, 970 1D4 (monoclonal antibody), 29 DNA-binding oligomer, 463 E Docosahexaenoic acid, 62, 64t E9.5, see Embryonic day 9.5 (E9.5) Dodecyl octaethylene glycol ether (C12E8), 6 Earley, S., 718, 765 Dopamine transporter (DAT), 997 EC50, see Half efficiency activation (EC50) Dörr, J., 909–922 ECaC, see Epithelial Ca2+ channel (ECaC) Dorsal horn neurons (DHN), 604, 620 E. coli, see Escherichia coli (E. coli) Dorsal rhizotomy, 618, 620 E. coli chemotaxis receptor, 462 Dorsal root ganglia (DRG), 44, 51–53, 55, 60, Econazole, 94–95, 711t 66, 71, 186, 196, 198, 332, 475, Ectoparasites, 366 479, 493, 539–540, 580, 583, bugs (bedbugs), 366 616, 618, 626, 628, 637, 639, head lice, 366 863, 863t, 867–868, 989 pea aphid, Acyrthosiphon pisum, 366 1046 Index

Ectoparasites (cont.) 2D crystal, 6 ticks, 366 2D sheet, 5 trpA1 (ISCW011428) in I. scapularis, 366 Electron microscopy (EM), 3, 28, 30, 32, 34 TRP channel genes/D. melanogaster, structures, features, 34 comparison, 366, 367t conductance pore, 34 Ectopic TRPV1 expression, 950 gate, 34 EDTA-AM (cell-permeant magnesium ligand-binding site, 34 chelator), 175 selectivity filter, 34 Edwards, M. K., 324 TRP channel structures EET, see Epoxyeicosatrienoic acid (EET) imaged in ice, 31 E3 extracellular domain, 114 imaged in negative stain, 31 EF-hands TRPC3, 31 Ca2+ binding vs. non-Ca2+-binding, 18 TRPM2, 31 Ca2+ coordination, 17 TRPV1, 31 affinity, 17 TRPV4, 31 canonical vs. non-canonical (atypical), Electrophilic cyclopentane prostaglandin 17–18 D2 metabolite, see 15-Deoxy- 12,14 NMR structure in TRPP2 C terminus, 18f -prostaglandin J2 TRPA1, 18 (15d-PGJ2) TRPML1, 18 Electrophysiological and photoaffinity labeling TRPP2, 18 experiment, 377 EGF, see Epithelial growth factor (EGF) Electrophysiological recording, 96, 119, EGFP expressing mice, TRPV5 promoter 225–226, 332, 343, 437, 524, driven 645, 910 mouse generation, 279–280 Electrophysiology, 50, 107, 118, 139, 175, genomic organization of TRPV5 gene 342, 423, 645, 813 and constructs, 280f Electroretinogram (ERG), 141 restriction enzyme NaeI, 280 Elke, L., 637–656 SalIandAgeI restriction sites, 279 EM, see Electron microscopy (EM) TRPV5-EGFP DNA, 280 Embryo implantation process, 252 wild-type C57Bl/6 x DBA2 F2 hybrid Embryonic day 9.5 (E9.5), 174 mice (B6D2F2), 280 Embryonic stem (ES) cells, 174, 279 studies in TRPV5-EGFP mice, 281–283 Emerging roles in neuronal function EGFP expressing tubules, functionality activation mechanism, 574f + of, 281 Ca2 influx, 574 intracellular Ca2+ signalling, 282 physiological importance, TRPC validation of transgenic mouse lines, TRPC1, 576–578 280–281 TRPC2, 578 differences of transgene expression, TRPC3, 578–582 280 TRPC4, 582–583 EGFP expression in DCT2/CNT/CCD, TRPC5, 581–582 280–281, 282f TRPC6, 582–584 flow chart of, 281f TRPC7, 584 TRPV5-EGFP transgenic mice, founder TRPC channels and oxidative stress lines (F0), 280 participation in SH-SY5Y cells, 586 EGF receptor, 234, 294, 550, 715, 795 TRPC proteins in neurodegenerative EGFR-PKCα-ERK signaling pathway, 55 diseases Eicosapentaenoic acid, 62 BDNF treatment, 585 2+ EJ (urothelial cell line), 956 [Ca ]i concentration, changes, 585 El Boustany, C., 678 neuroprotective effect, 585 Electro-mechanical coupling, 708 neurotoxins, 585 Electron cryo-microscopy (cryo-EM), 5–7, 9, phosphoinositol pathway, activation, 33 585 Index 1047

E830 mutation, 156 Epinephrine, 669, 891 Endocannabinod anandamide, 953 Epithelial Ca2+ channel (ECaC), 240, 917 Endocannabinoid-inactivating enzyme, 992 Epithelial growth factor (EGF), 550 Endocannabinoids, 117–118, 582, 627, 764, receptor, 294, 329, 548t, 715, 890, 932, 914–915, 990, 992, 997 949, 977 Endoparasites Epithelial sodium channel (ENaC), 257, helminths, 361–366 278, 332, 839, 863t, 864f, 865, protozoa, 362–363 869–870 Endoplasmic reticulum (ER), 28–29, 91f, 92, Epitope affinity chromatography, 30 99, 158, 187, 294–295, 297, 299, ePKC, see Eye specific protein kinase C 350, 375f, 393, 414, 436 (ePKC) Endoplasmic reticulum (ER)-associated EPO, see Erythropoietin (EPO) receptor protein degradation pathway, E. poissonii, 51 350 Epoxyeicosatrienoic acid (EET), 61, 94, 548t, 2+ Endoplasmic reticulum (ER) ([Ca ]er) 552, 559, 693, 695, 697, 764, metabolism of xenobiotic compounds, 669 822 protein synthesis, 669 E1047Q substitution, 153 2+ Endothelial [Ca ]i homeostasis, 764 ER, see Endoplasmic reticulum (ER) Endothelial cell, 90, 533, 667 ERG, see Electroretinogram (ERG) migration, 795 Erk, see Extracellular signal-regulated kinase dysfunction, 533 (ERK) Endothelial NO synthase (eNOS), 377–379, ERM, see Ezrin/radixin/moesin (ERM) domain 379f, 793 ER marker, 558 Endothelin-1 (ET-1), 404, 697, 787f–788f, ER-PM microdomains, 440 787, 789, 799 Erythropoietin (EPO) receptor, 127, 130–131, Endovanilloid, 94, 990 885, 890 5-lipooxygenase and 12-lipooxygenase Erythropoietin-evoked calcium signalling, 130 products, 54 Escherichia coli (E. coli), 6, 241, 452 leukotriene B4, 54 chemoreceptors 12-S-HPETE, 54 Tar, 457 End-stage renal disease (ESRD), 289 Tsr, 457 Enolized α-dicarbonyl system, 96 HB101, 456 eNOS, see Endothelial NO synthase (eNOS) temperature-controlled switching Enthalpy value (H(TR)), 460 clockwise (CW), 457 Entropy value (S(TR)), 460 counterclockwise (CCW), 457 Envenomation, 54 thermoreceptors Enzymatic de-glycosylation, 29 Tap, 457 Epidermal keratinocytes Trg, 457 TRP expression, 847–849 ET-1, see Endothelin-1 (ET-1) Calcium imaging, 849f ETA receptor, 404 environmental factors, 854–856 ETB receptor, 404 immunostaining of human epidermis, Eucalyptol, 192, 630 848f treatment putative skin surface sensory system., muscular pain, 198 848f rhinosinusitis, 198 TRP’s role in, 849–850 Eucalyptus sp. (eucalyptol), 62 low pH, activation, 850–851 Eugenia caryophyllata, 45t, 50 skin inflammation, 850 Eugenol, 45t, 50, 59–60, 62, 70, 188, 190t, Ultraviolet (UV) radiation, 851 330, 627, 853 Epidermal permeability Eukaryotic proteins TRP’s role advantages, 28–29 barrier homeostasis, 851–853 Baculovirus-mediated expression, 28 Epilepsy, 603 crystallization, 27 1048 Index

Eukaryotic proteins (cont.) Expression cloning approach/technique, E. coli expression, 27 43–44, 62, 240 Golgi apparatus, 29 Expression pattern and biological function, insect cell expression, 28 TRPV1 protease-deficient strain, 29 modulation of expression recombinant protein, expression, 28 extracellular matrix (ECM) molecule, rough endoplasmic reticulum, 29 640 vector expression, 29 fibronectin, 640 E. unispina, 51 HEK cells, 640 Euphorbiacea, 61 increased expression, 640 Euphorbia resinifera, 45t, 51, 481 native cells, 640 Euphorbiengummi resinifera (resiniferatoxine), physiological and pathological roles 98 deoxycortisosterone acetate treatment, Everett, K. V., 1011–1027 641 Evodiamine elicit respiratory defense responses, 641 biological effects, 55 pain and temperature sensation, 641 adipogenesis inhibition, 55 respiratory diseases, 640–641 cancer cells, increased apoptosis, 55 urinary bladder, 641 capsaicin-like effect, 55 vascular and renal hypertension, 641 capsazepine-sensitive contraction, 55 tissue distribution Evodia rutaecarpa (Chinese herb), 55 epithelial cells in human airways, 639 Evolution, TRP channel, 350–351 hematopoietic cells, 639 chordate phylogenetic tree, 351 liver, 639 mammalian thermoreceptors, 350 skin, 639 urochordates, 351 smooth muscle of bladder, 639 warm-blooded animals, 351 Extracellular hypotonicity, 94 Exogenous OAG, 396, 401 Extracellular signal-regulated kinase (ERK), Expression and function in liver cells 347, 375–376, 381, 381f, 769, ectopic expression, 673 794, 936, 954–955 in other cell types present in liver Eye specific protein kinase C (ePKC), 395, liver endothelial cells, 677 554–555 polycystic liver disease development, Ezrin/radixin/moesin (ERM) domain, 127, 677 419t, 422, 441 PRKCSH mutations, 677 vascular smooth muscle cells, 677 F physiological functions Faecal incontinence, 640t TRPC1 and volume control, 674–675 FAK, see Focal adhesion kinase (FAK) TRPM7 and cell proliferation, 675 Familial hyperkalemia and hypertension TRPML1 and lysosomal Ca2+ release, (FHH), 256 675–676 Faraday’s constant, 461, 473, 518 TRPV1 and TRPV4 in cell migration, Farfariello, V., 947–961 674 Farnesyl pyrophosphate (FPP), 58t, 60 store-operated Ca2+ entry in hepatocytes activation, 60 ectopic expression, 673 GPR92 membrane receptor, 60 with SERCA inhibitors, 673 inhibition, 60 SOCs in liver cells, 673 LAP2 receptor, 60 TRP channels and liver cancer LAP3 receptor, 60 with chronic hepatitis, 678 Farnesyl thiosalicylic acid (FTS), 485 with cirrhotic livers, 678 Fas-associated factor-1, 951 mRNA expression, 678, 679f Fas/CD95, 950, 951, 952f thapsigargin-initiated Ca2+ entry -associated protein, 951 increased, 678 -induced apoptosis, 955 TRP channels expressed in liver, 671t–672t Fasciculol C-depsipeptide, 52 Index 1049

Fatty acid amide hydrolase (FAAH), 893, FSGS5 on chromosome 14q32.33, 1012 992 FSGS2 on chromosome 11q21-q22, Fatty acid synthase (FASN), 302 1012–1013, 1013f Fecher-Trost, C., 909–922 Formalin-induced nociceptive response, 50 Fenton, R. A., 277–285 Forskolin, 497–498, 548t, 557–558, 563 Ferrer-Montiel, A., 491–509 Fourfold rotational symmetry, 7 Feske, S., 415 FPP, see Farnesyl pyrophosphate (FPP) FFA, see Flufenamic acid (FFA) 680–796 Fragment, 19 FGF, see Fibroblast growth factor (FGF) 720–797 Fragment, 19 FHH, see Familial hyperkalemia and Frankincense, 60 hypertension (FHH) Frictional damping, 461 Fibroblast growth factor (FGF), 247, 576, 768, Friis, S., 120 796, 988 Frog/zebrafish model systems, TRP ion Fibrosis, 180, 755, 798, 971 channels using, 341–352 Field potential recording, 128 cyst formation in mammals/zebrafish, FK506-binding protein 52 (FKBP52), 344 348–349 FLIPR, see Fluorometric Imaging Plate Reader expression of TRP channel, 344–345 (FLIPR) Map kinase activity, TRPC1 regulation, Flockerzi, V., 737 347–348 Flores, E. N., 221–228 RPN1, zebrafish functions of, 345–346 Fluconazole, 95 tissue-culture model hypothesis, 349–350 Flufenamic acid, 156 TRPA1, noxious chemicals, 346–347 activation TRP channel evolution, 350–351 TRPA1, 156 TRPC1 in frog oocytes, 341 TRPC6, 156 TRPM7 in embryonic development, common chloride channel blocker 2+ − 351–352 Ca -activated Cl channel, 156 TRPV4/TRPP2, heteromultimer of, 349 proton-activated Cl− channel, 156 − Xenopus embryogenesis, TRPC1 in, swelling-activated Cl channel, 156 343–344 inhibition FRTL-5 cell, 126, 130, 131f TRPC3, 156 Fructooligosaccharide, 249 TRPC5, 156 Füchtbauer, E.-M., 277–285 TRPM2, 156 Functional magnetic resonance imaging PBC inhibition, firing rate reduction, (fMRI), 991 161 Functional studies, Budding Yeast, 25–35 Flufenamic acid (FFA), 113f, 113, 156, 161, Functional TRPV1 channel, 953–954 602, 711t, 715, 735t, 890 Function of temperature, 461 Fluorescence resonance energy transfer (FRET), 175, 227, 349, 421, Fura-2, 29, 673, 750, 821f 423, 440, 478, 524, 533, 557, Furini, S., 485 769, 786, 886 Future prospect, TRPV1 Fluorescent Ca2+ assay, 52 antibodies and toxins, biologics Fluorometric Imaging Plate Reader (FLIPR), E3 loop, 655 645–646, 648t venomous animals, 655 fMLP, see N-formyl-Lmethionyl-L-leucyl-L- modality specific TRPV1 antagonists phenylalanine (fMLP) A-425619, 655 Focal adhesion kinase (FAK), 581–582 AMG-0610, 655 Focal cerebral ischemia, 580 AMG-6880, 655 Focal segmental glomerulosclerosis (FSGS), AMG-7472, 655 347, 1012 AMG-8562, 655 FSGS3 on chromosome 6p12, 1012 AMG-9810, 655 FSGS1 on chromosome 19q13, 1012 BCTC, 655 FSGS4 on chromosome 22q12, 1012 SB-366791, 655 1050 Index

Future prospect, TRPV1 (cont.) role, 402–404 structure-guided drug discovery TRPC1-containing channel activity, insect cells, 655 403 mammalian cells, 656 PKC-activated channels, 402–404 yeast, 655 epidermal growth factor, applications, 403 G role, 403 GABAergic inhibitory postsynaptic currents, See also Diacylglycerol (DAG) 998 Gaultheria, 49t, 55, 68t Gadolinium ion, 93, 98–100 G1 cell cycle phase, 178, 950 Gailly, P., 126 Gαq-coupled muscarinic receptor, 177 + Gain-of-function mutagenesis analysis, 35 Gd3 , 299, 318, 328, 435, 442–443, 642, 711t, Gain-of-function mutation, 232, 234, 1012 735t–736t, 750, 870, 920, 937 Gain-or loss-of-function phenotype, 35 Gel ﬁltration, 30 Gαi2 subunit, 127 Generic gating mechanism, 35 Galectin 1 (GAL1), 247, 934, 958 Genes (TRP) and human inherited disease, Galectin-1 linked TRPV5 protein, 247 1011–1027 Gambierol, 54 canonical TRPs, 1012 Gamma-aminobutyric acid (GABA), 580, 995 congenital stationary night blindness, García-Añoveros, J., 221–228 1017–1019 Garland, C. J., 761–763 HSH, 1020–1022 Gastric adenocarcinoma cell, 178 polycystin TRPs, 1023 Gastro intestinal tract and TRP Kozlowski type spondylometaphyseal in intestinal motility, 697–698 dysplasia, 1015–1016 TRP in intestinal motility, 697–698 metatropic dysplasia, 1016 TRPM8 and gatric activity, 698 neuromuscular disorders Gating currents, 519 melastatin TRP, 1017 Gating mechanism progressive familial heart block, type 1B, diverse group of functional channel 1020 isoforms, 392–393 skeletal disorders, 1014 amino acid residues, 392 TRPC6, 1012–1013 heteromeric structures, 392 vanilloid TRPs, 1013 homomeric structures, 392 TRPM1, 1017 proposed functional heteromeric TRPM4, 1020 channel structures, 393t TRPM6, 1020 voltage-gated channels, 392 TRPML1, 1025–1027 Drosophila photoreceptors, 395, 397f TRPP1=PKD2, 1023–1025 2+ IP3-mediated release of Ca , 395 mucolipin TRPs, 1025 Drosophila TRP channels, activation, TRPV4, 1014 394–397 type 3 brachyolmia, 1014–1015 DAG, central role, 395–397 Geraniol, 62, 64t, 188, 190t Drosophila TRPL channels, activation, Gαθ/Gα11 protein-coupled receptor, 393, 401 394–397 Gibbs energy, 458, 460, 472 DAG, central role, 395–397 zero point crossing of mammalian non-TRPC1- and high temperature (heat denaturation), TRPC1-containing channels, 460 399f low temperature (cold denaturation), photon absorption, 395 460 physiological channels, 393–394 Gibson, H. E., 993 SOC protein, activation, 393 Giga-ohm patch clamp recording, 107 subunits as ROCs and SOCs, 394 Gilbert Ling, 461 PIP2-activated channels, 402–404 Gingerol, 50–51, 70 Ca2+ entry mediation, PI role, 404 6-Gingerol, 45t, 51 Index 1051

8-Gingerol, 45t, 51 Grid cells, 596 GlaxoSmithKline, 621, 652t Grimm, C., 713 Gleason score, 254, 262, 933, 959 GRM6 gene, 141 Glenmark, 646, 650t, 652t, 653 Growth cone morphology, 43, 378, 581, 996 Glibenclamide, 157, 164, 814 Growth cone steering, 581 Glioblastoma, grade IV, 935, 952 Growth receptor channel (GRC), 231, 650t, Glioma cells, 932, 935, 952, 955, 957 652t, 653, 954 Glomerulus/glomeruli, 277, 294, 345, 1012 GSK1016790A (TRPV4-selective agonist), Glucagon, 669, 819 89f, 98, 822, 978 Glucocorticoid-induced osteoporosis GsMTx-4 peptide, 71, 72t mechanism, 257 GST-fused N-terminal splice variant, 138 Glucocorticoids, 177, 254, 257–258, 506, 561, Gαo subunit, 127 740, 975, 991 GTPase ADP-ribosylation Factor 6 (Arf6) β-Glucuronidase, 246–247, 548t, 562 pathway, 226 β-Glucuronidase Klotho, 560 Guaiacol, 45t, 50 Glu994 residue, 381 Guaiacum, 45t, 50 Glutathione peroxidase, 532 Guamanian ALS and PD case, 382 Glutathione S-transferase, 738 Guamanian amyotrophic lateral sclerosis, 175, Glycine-rich GXA(G)XXG motif, 10–11 537 Glycogen synthase kinase 3 (GSK3), 295, 564 Guamanian amyotrophic lateral sclerosis Glycosidase klotho, 934 and parkinsonian dementia Golgi, 29, 214, 226, 295, 319, 378, 507, 559, (ALS/PD), 175, 537 564–565, 670f, 890 Gudermann, T., 781–800 Golgi protein RNF24, 549t, 553, 890 Guibert, C., 687–699 González-Nilo, Dr. F., 486 Guinamard, R., 814 Gordon syndrome, 256 Guinea pig airway SM cells, 732, 736, 739 Gottlieb, P., 800 Guinea pig airway smooth muscle, 974 Gouy-Chapman-Stern equation, 480 GPCR, see G-protein coupled receptor (GPCR) H Gαo-protein, 140, 142 3H-A-778317, 645 G-protein-coupled PLC pathway, 402 Habener, J. F., 814 G protein-coupled receptor proteolytic site Hahn, M. W., 260 (GPS), 293–294, 301 Half efﬁciency activation (EC50), 44, 45t–49t, G-protein coupled receptor (GPCR), 327, 50–56, 57t–58t, 59–62, 63t–64t, 948–949 66, 67t–68t, 69–71, 72t, 89f, + and Ca2 store depletion, roles of, 713–714 115, 116f–117f, 154–155, PIP2-binding domains, 714–715 189t–190t, 195t, 499, 502, 653, TRPM4/5/7/8, 715 814–815, 820–821 vasoactive agonists (angiotensin Half maximal inhibition (IC50), 55, 59, 65, 91, II/bradykinin/aldosterone), 715 94, 156 G protein gustducin switch, 163 Hallmark helix-loop-helix fold, 17 G-protein inhibitor GDP-β-S, 599 Hanahan, D., 930 Gq-coupled receptor agonist, see Vasopressin HAPMAP database, 136 Gq/Go-protein, 56, 936, 955 Hara, Y., 94 Gq/11/phospholipase C (PLC) coupling, 709, Hardie,R.C.,99 715 Harteneck, C., 87–100 Grammostola spatulata (Chilean Rose Hb, see Hemoglobin (Hb) tarantula), 71, 72t HC-030031, 625, 766, 972 Gram-negative pathogenic bacteria, 163 H19-7 cells, 576–577, 579, 584 Grandl, J., 477–478 HCN channels, 162, 524, 526 GRC-6211, 650t, 653 HCTZ, see Hydrochlorothiazide (HCTZ) Greka, A., 378 Heart tube looping, 177 G805 residue, 186 Heat capacity change (Cp), 460 1052 Index

Heat sensitive TRPs, see Thermo TRP channels He, Y., 719 Heat shock protein (HSP), 452 HIF-1, see Hypoxia-inducible factor 1 (HIF-1) Hebeloma senescens (hebelomic acid), 47t, 52 H4-IIE rat liver cells, 671t–672t, 674, 678, 931 Hebelomic acid A, 52 Hippocampal neuron, 94, 344, 547, 550–552, Hebelomic acid B, 52 579, 581, 583–584, 586, 882, Hediger, M. A., 254 996 HEK cell, 134, 229–230 His958 residue, 381 HEK-293 cell, see Heterologous expression Histidine residues system (HEK-293 cell); Human His252, 233 embryonic kidney (HEK-293) His273, 233 cell His283, 233 HEK293 cell line, 234 Histone H2A.Z, 456 HEK-293T cell, 177, 586 HMBA, see Hexamethlene bisacteamide HEK293-TRPM3 cell, 114 (HMBA) HeLa cell, 211t, 214, 226, 553 HMVEC, see Human microvascular HeLa cell line, 234 endothelial cell (HMVEC) Helix-loop-helix leucine zipper transcription H934N mutation, 156 factor, 137 H–NS (bacterial protein), 456, 464 Helminths H2O2 application, 379–380 nematodes, 363–365 9-HODE, see 9-Hydroxyoctadecadienoic acid trematodes and cestodes, 365–366 (9-HODE) Hemoglobin (Hb), 458, 464, 471 13-HODE, see 13-Hydroxyoctadecadienoic Hensen’s cell, 230 acid (13-HODE) Hepatic stellate cells, 667 Hodgkin, A. L., 519 Hepatocyte, 113, 178, 549t, 667, 668f, Hoenderop, J. G., 240, 279 669–670, 670f, 671t–672t, Hofherr, A., 287–303 672–678, 932, 935, 952 Hofmeister, M. V., 277–285 Hepatocyte [Ca2+] , changes cyt Hogstrand, C., 242 amino acid, 669 Homeoviscous adaptation, 454 apoptosis and necrosis, 669 Homer 1, 127, 505, 753, 756 bile acid secretion, 669 cell cycle and cell proliferation, 669 Homology modeling method, 33 fatty acid, 669 Homo-oligomer, 464 glucose, 669 Homotetrameric channel, 186, 795 lysosomes movement, 669 Homotetrameric glutamate-gated receptor protein synthesis and secretion, 669 channel, 16 xenobiotic metabolism, 669 Homotetramers, 16, 30, 186, 532, 534, 710, Hepatocyte growth factor/scatter factor 795, 934, 958 (HGF/SF), 952–953 Homozygote knockout clone, 178 Hepatoma cell, 178, 931 Hormone–refractory prostate cancer, 200 HepG2 cell, 674, 678, 936, 957 Horseradish, 66 HepG2 cells hepatoblastoma cells, 957 Host-defense mechanism, 53 Hereditary motor and sensory neuropathy Hot receptor (TRPV1), 477 type IIC (HMSN2C), 1015t, Hot water bath hand withdrawal time (HWT), 1016–1017 653 Herson, P. S., 811 Høyer, H., 285 19-HETE-DA, 48t, 54 HPAEC, see Human pulmonary artery 20-HETE-DA, 54 endothelial cells (HPAEC) Heteractis crispa, 48t, 54 HPV, see Hypoxic pulmonary vasoconstriction Heterologous expression system (HEK-293 (HPV) cell), 50, 52, 119, 162, 233, 508, 3H-resiniferatoxin, 52–53, 644–645 536, 783, 800, 977 [3H]resiniferatoxin (RTX), 989 Hexamethlene bisacteamide (HMBA), 139 3H-RTX binding, 52, 55 Index 1053

HSH, see Hypomagnesaemia with secondary Hydroxy-α-sanshool, 68t, 69–70 hypocalcaemia (HSH) 20-Hydroxyeicosatetraenoic acid, 71, 735 HSP, see Heat shock protein (HSP) 4-Hydroxynonenal (4-HNE), 69, 623, 972 Huang, C. L., 561 9-Hydroxyoctadecadienoic acid (9-HODE), 54 Huang, G. N., 421–423 13-Hydroxyoctadecadienoic acid (13-HODE), Hu, H., 93 49t, 54 Hu, H. Z., 851 9-Hydroxyphenanthrene (9-Phenanthrol), 157 Huber, A., 545–566 25-Hydroxyvitamin D (25(OH)D), 245 Hughes, D. A., 260 Hyperalgesia, 54, 66, 197–198, 492, 494, Hughes, J., 300 503–504, 557, 616–621, Huh-7, 671t–672t, 678, 679f 624–625, 627–628, 648t–650t, Hui, K., 481 868, 951t, 990, 999 Human embryonic kidney (HEK) cell, 837, Hypercalciuria, 248, 256t, 257, 259, 262, 918 1014 Hyperforin, 71, 72t, 90, 92f, 95, 95f, 96, 850, Human embryonic kidney (HEK-293) cell, 891, 991 151, 153 Hypericum perforatum (St John’s Wort), 71 Human glomerular mesangial cell, 403 Hyperphorin, 582 Human islet amyloid polypeptide (hIAPP), Hyperthermia, 98, 201, 621, 652t, 653–656 822 Hypertrophic process, 162 Human lung epithelial cell, 187 Hypoalgesia, 998 Human melanoma, 138–139, 200, 937 Hypocalciuria effect, 258–259 Human microvascular endothelial cell Hypoglutamatergic hypothesis, 995 (HMVEC), 768, 791, 795, Hypomagnesaemia with secondary 887 hypocalcaemia (HSH), 784, Human pancreatic cancer, 935, 952 1020–1022 Human peripheral bloodacute lymphoid compound heterozygosity, 1021 leukemia (HPB-ALL), 931 deletion of exons, 1021 Human prostate cancer xenograft tumor, magnesium deﬁciency, 1020 201 mapped to chromosome 9q21.13, 1020 Human Protein Atlas, 821, 823 missense mutations in TRPM6 protein, Human pulmonary artery endothelial cells 1021, 1022t (HPAEC), 550, 760, 795 polycystin TRPs, 1023 Human umbilical vein endothelial cell adult polycystic kidney disease (HUVEC), 768, 792 (ADPKD), 1023 Human urothelial cancer, 935, 950, 958 PKD1, PBP (polycystic breakpoint), Huque, T., 837 1023 HUVEC, see Human umbilical vein endothelial TRPP1 (or PKD2), 1023 cell (HUVEC) TRPP2 (PKD2L1 or PKD2-like 1), Huwentoxin 5 (HwTx-V), 53 1023 Huxley,A.F.,519 TRPP3 (PKD2L2 or PKD2-like 2), HwTx-V, see Huwentoxin 5 (HwTx-V) 1023 Hydra, 230 S141L mutation, 1021 Hydration, 460 W1925W in Turkish family, 1021 Hydrochlorothiazide (HCTZ), 256t, 258 Hypomagnesemia, 175, 255t, 329, 714, 773, Hydrogen bonding, 460 784, 793 Hydrogen peroxide (H2O2), 65, 88, 90, 92, Hypotension, 278, 641 94–95, 95f, 99, 456–457, 532, Hypoxia-inducible factor 1 (HIF-1), 798 536, 769, 795 Hypoxic pulmonary vasoconstriction (HPV), Hydroperoxyeicosatetraenoic acids (HPETE), 695, 798 646, 990, 997 acute hypoxia, 695 Hydrophobic amino acid residues, 440 diacylglycerol (DAG), 695 Hydrophobic effect, 460, 524 roleofTRPC6inHPV,695 Hydrophobic nucleus, 461 SOC-mediated Ca entry (SOCE), 695 1054 Index

Hypoxic pulmonary vasoconstriction (cont.) Integral transmembrane topology, 230 and TRP, 695 Integrin/Src tyrosine kinase pathway, 628 acute hypoxia, 695 Intersectin, 549t, 560 diacylglycerol (DAG), 695 Interstitial cells of Cajal (ICCs), 698, 863t, roleofTRPC6inHPV,695 864f, 865–866 SOC-mediated Ca entry (SOCE), 695 Intestinal motility, TRP in, 697–698 Hysteresis, 59 gastro intestinal motility, 698 parasympathetic signalling, 697 I TRPC4-, TRPC6-, and TRPC4/TRPC6- Iberiotoxin, 733 gene-deﬁcient mice, 698 Ibuprofen, 627 TRPC4-/TRPC6-/TRPC4/TRPC6-gene- deﬁcient mice, 698 IC50, see Half maximal inhibition (IC50) Intracellular Ca2+ concentration ([Ca2+] ), ICaNS, see Non-selective cation current (ICaNS) i Icilin, 114–115, 186–188, 189t, 194, 196–198, 128, 279, 378, 505, 601–602, 201, 373, 626, 716, 720, 722, 675, 694, 699, 835f, 939, 1012, 863t 1016 Icillin, 88, 97, 475, 480–481, 793 Intracellular desensitization process, 97 ICK, see Inhibitory cysteine knot (ICK) Intracellular signalling pathways cytoplasmic Ca2+ increases, 674–675 ICRAC, see Calcium-release-activated current IP3, 674–675 (ICRAC) Idiopathic detrusor overactivity, 197, 863–864, phospholipase C, 674–675 867 Intra-nasal nicotine, 973 Idiopathic pulmonary arterial hypertension Intrinsic pacemaker activity, 161 (IPAH), 797 In vitro cultivation temperature, 453 I331F mutation, 14 In vitro cultured cardiomyocyte, 376 IGF-1/IGF-1R pathway, 954 In vitro model, 162 IMCD-3, see Inner medullary collecting duct In vivo model, 162 (IMCD-3) In vivo rodent model, 179 Immunohistochemistry approach, 243 Iodoresiniferatoxin, 97–98, 197, 790, 996 Immunoprecipitation, 227, 302, 344, 349–350, Ion channel properties 374, 378, 399–400, 443, 505, activation 533, 738, 753, 786, 911t, 916t, heat, 641 920t low pH, 641 InaC gene, 395 vanilloid compounds, 641 INAD, 554 voltage, 641 Incensole acetate, 60, 994 function modulation Inducible deletion system, 178 N-glycosylation, 644 Inhibitory cysteine knot (ICK), 53 PIP2 hydrolysis, 643 Initial part of the cortical collecting duct gating biophysics (iCCD), 278, 281 Ile696, Trp697, and Arg701, Inner medullary collecting duct (IMCD-3), substitution, 643 551–552 lower conductance (50 pS), 642 Inositol triphosphate (IP3), 31, 43, 156, 550, ion selectivity and permeability 883, 887, 894 activated with capsaicin, 643 Inositol 1,4,5-trisphosphate (IP3), 91f, 92, 99, Asp646, 643 374–377, 417, 424f, 533, 694, neutralization, 643 709, 735t, 739, 895 S800A mutation, 643 Inoue, R., 694 Tyr671, 643 Insulin, 113, 149, 158–160¸278, 381–382, 504, Ion channels, 25, 27, 960 548t, 551, 555, 557–558, 669, chemical signals, 25 752–754, 812, 813t, 814–819, cryo-EM determinnation channels, 31 821–824, 954 inositol triphosphate receptor, 31 Insulin/IGF-1, 548t, 557 large-conductance calcium-channel, 31 Index 1055

muscle calcium release chan- in stimulus-secretion coupling in nel/ryanodine receptor (RyR1), β-cells, 815–816 31 TRPM2 (LTRPC2) muscle L-type voltage gated calcium and β-cells, 817 channel (dihydropyridine and β-cells death, 820 receptor), 31 heat, 819 + voltage-activated potassium channel intracellular Ca2 release channel, 820 (BK), 31 in stimulus-secretion coupling in voltage-gated channel KvAP, 31 β-cells, 817–818 voltage gated sodium channel, 31 TRPV1, 823 determination mechanisms TRPV2, 822–823 channel gating, 25 TRPV4 (OTRPC4/VR-OAC/VRL-2/TRP- ion selectivity, 26 12), 821–822 modulation, 26 Isothiocyanate, 66 forms, 66 permeation, 26 allyl, 66 electrical signals, 25 benzyl, 66 mechanical signals, 25 isopropyl, 66 selectivity and permeation, characterization methyl, 66 tools, 87–88 phenylethyl, 66 divalent cation, 87 Isothiocyanates (mustard oil), 623 trivalent cation, 87 Iti, see Transient inward current (Iti) single-particle analysis work, 31 IV, see Current-voltage (I–V) relationship temperature signals, 25 I–V curve, 180, 712 Ion channel translocation, 545–565 Iwata, Y., 754 Ion ﬂux, 31, 547, 882 IonWorks (MDC), 108, 645 J IonWorks Quattro, 109 J82 (urothelial cell line), 956 IP3, see Inositol triphosphate (IP3); Inositol Jacobsen, R. B., 107–120 1,4,5-trisphosphate (IP3) Jardín, I., 412–425 IPAH, see Idiopathic pulmonary arterial Jaw-opening reﬂex, 622, 623f hypertension (IPAH) Jiang, J., 177 IP3R, 609 Jiang, Y., 263, 561 Jiménez-Díaz, L., 595–606 See also IP3 receptor (IP3R) Jing, H., 263 IP3 receptor-independent mechanism, 400 JNJ17203212, 641 IP3 receptor (IP3R), 71, 72t, 91f, 92, 127, 130, 163, 326, 375f, 376, 395, JNJ-39267631, 193f, 194, 197 398, 400–402, 417, 422–423, JNK, see c-Jun N-terminal kinase (JNK) 436, 574f, 601, 670, 674, 764, Johnson, C., 707–723 783f–784f, 834, 887 Jordt, S. E., 481 IR-spectroscopy, 458 JTS-653 (Japan Tobacco), 652f, 654 Julius, D., 43, 481, 847 Ischemia, 179–180, 531, 537–538, 580, 676, Jung, J., 499 717, 769–770, 789–790, 997 Jung, S. J., 615–629 Ischemia/reperfusion injury, 532, 537–538, Jungnickel, M. K., 130 790 Jurka T cell line, 160 Ischemic stroke, 164, 179, 539 JYL1421, 641 Islam, M. S., 811–825 Islet of Langerhans, 158 K Islets, TRP channels of, 811–824 Kajimoto, T., 373–382 of insulin-secreting cells, 813t Kainate glutamate receptor, 56 TRPC1 and TRPC4, 823–824 Kaleta, M., 315–320 TRPM3, 820–821 Kallikrein, 245, 548t, 560 TRPM4 and TRPM5, 817–818 Karashima, Y., 624 1056 Index

+ KATP , see ATP-dependent K channel (KATP ) Kv channels, 470, 476, 479, 486, 519–520, KATP channels, 158, 812 521f, 528 + KB-R7943, 738 Kv1.2 K channel, 7 KB-R9743, 738 Kv1 potassium channel, 196 21 kDa protein, 536, 537f Kv’s, canonical voltage-activated potassium 25 kDa protein, 536 channel, 468 K+ efﬂux, 765, 793f, 799 pore module (TM5 and TM6), 470 Kelvin scale, 472 voltage sensor module (TM1 to TM4), 470 Kemp, B. J., 331 Kwan, K. Y., 625 Keratinocyte, 44, 59–60, 139, 250t, 253, 438, Kyphoscoliosis, 1015–1016 620f, 627, 786, 847–856, 891, 932, 936, 956, 977 L K562 erythroleukemia cell, 934, 958 L273, 442 Ketoconazole, 95 L276, 442 Kheradpezhouh, E., 678 Lactarius uvidus (drimenol), 47t, 52 Kim, S. H., 460 Lactarius vellereu (isovelleral), 46t, 52 Kim, Y. H, 619 L-α-lysophosphatidylcholine, 29 Kim, H. Y., 622 Lamiaceae, 62, 64t α-Kinase, 4t, 10–11, 27, 34, 173, 178, 258, LAMP2 stain, 215 294, 375, 398–400, 404, 423, Lanthanum ion, 93, 98–99 538, 558–559, 565, 617, 735t, Large, Prof. W. A., 404 784, 819, 890, 893 L-arginine, 55 Kinetic model, 472f, 471, 481, 482f, 520, 525 Latorre, R., 467–484, 521, 525 Kiselyov, K., 209–217, 1025 Lauryldimethylamine-N-oxide (LDAO), 6 Kiyonaka, S., 373–383 Lazaro gene, 394 Klein, R. M., 501 Lazzeri, M., 935, 950 Klose, C., 87 LDAO, see Lauryldimethylamine-N-oxide Klotho (KL gene product), 247, 958 (LDAO) “Leaky” gene expression, 225 Knee joint swelling, 618 Leech, C. A., 814 Knock-in experiment, 216 Lehen’kyi, V., 929–940 Knudson’s model, 1025 Lehenkyi, V., 934 Kohler, R., 771, 796 Leishmania, 230, 358t, 360 Koike, C., 137, 142 Lessard,C.B.,586 Koizumi, S., 854 Leucine zipper, 137, 463 KO mouse/mice, 164, 227, 250t Lewis, R. J., 41–73 functional TRPM5 protein, lacking, 163 L712F, 261–262 Köttgen, M., 297–301, 351 Liao, Y., 424 Kozlowski type spondylometaphyseal Lidocaine, 624 dysplasia, 1015–1016 Lien, 260 kyphoscoliosis, 1015 Ligand-gated approach, see PatchXpress mutation (D333G), 1015 (MDC) R594H mutation, 1015 Light-induced signaling cascade, 98 Krautwurst, D., 87–99 Liljestrand, G., 798 KU55933, 951 Li, M., 1–19, 177 Kühn, F., 825 Liman, E. R., 129 Kumar, P. G., 881–895 Linalool, 62, 64t, 70, 188 Kumar, S. V., 456 Linear current voltage (I/V) relationship, 814 Kupffer cells, 672, 676 Ling, G., 459 Kupffer cells (macrophages), 667 Linolenic acid, 128, 395 Kurata, Dr. H., 528 Lipid aggregate, 32–33 Kv1.2, 5f, 7, 8f, 31f, 34, 53, 480f, 520, 521f, Lipid bilayer recording, 675 525f, 639 Lipid hydrolysis, 214 Index 1057

Lipid rafts, 188, 376, 422f, 423–424, 437, 477, Lysophosphatidylcholine (lysoPC), 56, 62, 533, 560, 600 552, 558, 795, 955 Lipofuscin buildup model, 215 Lysophosphatidylinositol (lysoPI), 56, 65, Lipophosphatidylcholine, 581 548t, 558, 936, 955 Lipoxygenase homology/polycystin, Lysophosphatidylserine, 65 lipoxygenase, atoxin Lysophospholipid (LPL/lysoPLs), 188, 714, (LH2/PLAT) domain, 293, 935, 955, 974 301 LysoPI, see Lysophosphatidylinositol (lysoPI) Lipoxygenase reaction, 93, 293, 301, 790, 990, Lysosomal-endosomal fusion, 212 997 Lysosomal ion homeostasis, 212f, 213 Lishko, P.V., 498 Lysosomal storage disease (LSD), 210, 213 Listeria monocytogenes, 977 Liu, X., 433–443, 824 M Liu, Y., 185–200 M-68008, 654 Liver, 62, 148, 186–187, 224, 281, 289–290, Magnesium homeostasis, 88, 178, 692, 709, 358t, 359, 639, 667–680, 886, 718–719 931–932, 977, 1023 Magnesium Inhibitable Current (MIC), 175 Li, Z., 141 Magnesium nucleotide-inhibited metal L-methionine, 55, 863t (MagNuM), 175 LNCaP, 200, 248, 254, 931, 933–935, 938, MagNuM, see Magnesium nucleotide-inhibited 953–955, 959, see Lymph metal (MagNuM) node carcinoma of the prostate Mahieu, F., 479 (LNCaP) cell line Main olfactory epithelium (MOE), 129 Local antifungal therapy, 95 Maitotoxin, 674–675, 816 Lock-and-key agonist binding, 66 Major histocompatibility complex class I LOE908, 88, 90, 94 (MHC-I), 227 Löf, C., 125–131 Maleimides, 478, 972 Long-term depression (LTD), 506, 556, 993 Malignant tumors, 948 Long-term potentiation (LTP), 490, 556, 547, Mammalian cell, 6, 28, 226, 299, 453, 532, 993 644–645, 656, 710 Loot, 771 Mammalian diaphanous-related formin 1 Loss-of-function mutation, 210, 231–232, 349, (mDia1), 294 786 Mammalian respiratory tracts, 640, 969 LOV-1, 293, 326, 329, 362t, 564 Mammalian thermoTRPs, 517 L1089P residue, 16 Mammalian TRP channels LSD, see Lysosomal storage disease (LSD) ANKTM (A), 532 L-type Ca2+ channel blocker verapamil, 978 canonical (C), 532 L-type Ca2+ channels, 251, 601, 737–738, melastatin (M), 532 742, 890, 894, 978 mucolipin (ML), 532 L-type Ca2+ current, 604 polycystin (P), 532 Lucas, P., 126 vanilloid receptor (V), 532 Lukacs, V., 500 Mammary glands, 224, 253, 301–302, 921 Lung filtration coefficient (Kf), 978 Mandadi, S., 499 Lyall, V., 839 Mantle cell lymphoma (MCL), 949 Lymph node carcinoma of the prostate MAPK, see Mitogen-activated protein kinase (LNCaP) cell line, 200, 936, (MAPK) 955, 959 Map kinase activity, TRPC1 regulation Lymphocytes, 96, 159f, 160, 178, 224, 226, expression pattern of zebrafish trpc6, 350, 372–375, 412, 435–436, 347–348 440, 443, 537, 673, 786, 788, fli:gfp transgenic line, 347 949 MO targeting trpc1 translation, 347 LysoPC, see Lysophosphatidylcholine VEGF, 347 (lysoPC) in zebrafish embryos, 347 1058 Index

Marcus, D. C., 252 TRPM Marine polyether, 54 TRPM2, 534–538 Marker of cell-type, TRP channel, 344–345 TRPM7, 538–539 olfactory sensory neuron (OSN), 344 TRPV ciliated OSNs, 344 capsaicin, 539 microvillous OSNs, 344 caspase-3 in DRG neurons, activation, zebraﬁsh transgenic lines, 345 539 Maroto, R., 343 Medler, K. F., 831–842 Maruyama, Y., 420 Medullary part of the cortical collecting duct M. arvesis (cornmint), 62 (mCCD), 278 Mast cell, 44, 161, 178, 436, 442, 445, 492, Melanaphy, D., 707–723 558–559, 673, 891, 976 Melanocortin-1 receptor (MC1R), 139 Mast-cell activation, 165 Melanosome, 139, 352 Mathes, C., 120 Melastatin (MSLN), 136 Matrix attachment region (MAR), 284, Melastatin-related TRP (TRPM), 88, 99 Matta,J.A.,526–527 Membrane depolarization, 154, 158, 162–163, Matveev, V. V., 461, 464 187, 374, 518–519, 582, McAlexander, M. A., 969–979 586, 738, 741, 764–765, 799, M-calpain, 177–178 813–814, 816, 818–819 MCF-7 breast cancer cell, 178, 254, 939 Membrane receptor, 17, 60, 90, 163, 436, 576, MCF-7 breast cancer cell line, 178, 939 886 McKay, R. R., 910 Membrane voltage (Vm), 127–128 MCOLN3 Mentha piperita (peppermint), 59, 62 mutant alleles, 231t, 231–232 Mentha pulegium (isopulegol), 62 Va/ + and Va/Va, of mice, 232 Menthol, 62, 88, 97, 186–188, 189t, 198, 470, Va mutation, 232 627 normal alleles, 231–232 synthetic derivatives See also Mucolipin-3 gene (MCOLN3); Coolact P, 188 TRPML3 Cooling agent 10, 188 Mcoln4, see Trpml4 Frescolat ML, 188 MCOLN1 (NG_015806, NM_020533) coding, WS-3, 188 210 as traditional methods, 198 MC1R, see Melanocortin-1 receptor (MC1R) Menthone, 62, 626 MDA-MB-231 cell, 254 Merck, 652t, 653 Mechanical (acoustic) stimulation, 234 Mergler, S., 938 Mechanical allodynia, 628 Merulius tremellosus (merulidial), 46t, 52 Mechanical membrane stretch, 71, 109 Meseguer, V., 95 Mechano-activation, 109 “Metabolic” model, 212f, 213 Mechanosensation, 43, 71, 88, 108, 234, 240, Metabotropic glutamate receptor (mGluR6), 294–295, 317–319, 325–330, 141–143, 161, 198, 552, 599, 332, 462–463, 539, 617, 625, 887 627, 692, 861–871, 883 Metalloproteinases (MMP), 948 Mechano-sensor, 463, 713 Metatropic dysplasia, 14, 61, 1016 Mechanotransducer, 17, 691, 770, 871 characteristics, 1016 Mechanotransduction, 14, 231t, 234, 327, 329, point mutations, 1016 345, 711t, 718, 862, 864f, 917 TRPV4 mutations, 1016 Medial entorhinal cortex layer V cells, 601 Methacholine, 736, 739 Mediators of oxidative stress 1-(β[3-(4-Methoxyphenyl)propoxy]-4- TRPC methoxyphenethyl)-1H- diacylglycerol (DAG), 533 imidazole hydrochloride, 89f, inositol 1,4,5-trisphosphate (IP3), 533 90 NO sensors, 533 Methyl-β-cyclodextrin (MBCD), 479 TRPC3/4, activation, 534 use of, 424 Index 1059

Methylnicotinate, 999 Monovalent cations, 26, 109, 114, 147–165, Methylsalicylate, 55 299, 316, 417, 485, 643, 688, Meyer, N. E., 554 712, 760, 764, 784, 814, 834, Meyer, T., 439 893, 920 mGluR6, see Metabotropic glutamate receptor Moonwalker (Mwk) mice, 579 (mGluR6) Morenilla-Pelao, C., 479 MHC-I, see Major histocompatibility complex Mori, Y., 96, 373–383 class I (MHC-I) Morpholino (MO), 345 Miao, X., 935, 953 Mouse MIC, see Magnesium Inhibitable Current TRPC2–/–, mating behaviour, 129 (MIC) TRPC2, splice variants Mice lacking TRPM4 channels, 975 mTRPC2α, 126 Michailidis, I., 19 mTRPC2β, 126 Miconazole, 94, 711t TRPC2a, 126 Microbial ion channels, 315–316 TRPC2b, 126 Micromanipulated pipette, 107 Mouse colon afferent fibers, mechanosensitiv- Microphthalmia transcription factor (MITF), ity, 618 137, 139–140, 937 Movement-induced nocifensive behavior, 618 Microsatellite, 998 MSLN, see Melastatin (MSLN) Microvillous OSNs, 344 Muallem, S., 422 TRPC2, 344 Mucolipidin group (TRPML), 88 V2R-type receptors, 344 Mucolipidosis type IV (MLIV), 209, 222, Midbrain dopaminergic mechanisms, 1026, 1027t 998 achlorhydria, 210 Migraine, 509, 621, 651, 652t, 653 Drosophila model, 210 Miller,B.A.,531–540 pathological manifestations MIN-6 insulinoma, 558 constitutive achlorhydria, 210 Minke, B., 98 corneal opacity, 210 Mishra, R., 675 MITF, see Microphthalmia transcription factor gastric acid secretion, decrease in, 210 (MITF) retinal degeneration, 210 2+ Mucolipin-3 gene (MCOLN3), 229–230, 231t, Mitochondrial matrix ([Ca ]mt) apoptosis, 669 231–232 ATP synthesis, 669 Mucolipins 1 to3, see TRPML1; TRPML2; citric acid cycle, 669 TRPML3 Mitogen-activated protein kinase (MAPK), Mucus secretion, 641, 977 178, 504 Multiunit microelectrode array, 128 Mitral layer of olfactory bulb, 584 Multivariate Cox regression, 951–952 MK-2295/NGD-8243, 653–654 Murine haematopoietic cell, 130 MLIV, see Mucolipidosis type IV (MLIV) Muscle fatigue, 752 MLIV fibroblast cell, 214 Muscular dystrophy in mdx mice, 754, 756 MMP2, 936, 955 Mustard oil, 69, 110, 188, 190t, 346, 548t, MMP9, 936, 955 563–564, 623, 766, 782, 863t Mn2+ entry assay, 175 Mutagenesis method, 16–18, 33, 35, 99, 342, Mochida Pharmaceuticals, 654 348, 351, 438, 477, 498, 524, MOE, see Main olfactory epithelium (MOE) 557, 560, 566, 579, 783 Mohapatra, D. P., 498 Myocardial ischemia, 790–791 Moiseenkova-Bell, V., 25–35 Myo-endothelial gap junction, 760 Molecular dissection of YVC1 Myofibroblasts, 180, 641, 789, 864f, 866 (TRPY1), 318 Myogenic tone and TRP, 694–695 Monet, M., 558 calmodulin and myosin light chain Monod, J., 481–482 kinase, 694 Monoterpenoid linalool, 70 mammalian TRP isoforms, 694 1060 Index

Myogenic tone and TRP (cont.) mechanosensation, 43 TRPC6 antisense oligodeoxynucleotides, osmotic pressure, detection, 43 694 thermosensation to vasoregulation, 43 TRPC6–/– mice, 694 mammalian subfamilies TRPM4-like channels, 694–695 TRPA (Ankyrin), 43 TRPV2, 695 TRPC (Canonical), 43 Myoglobin, 461, 464 TRPML (Mucolipin), 43 Myosin II, 11, 784 TRPM (Melastatin), 43 TRPN (No mechano-potential), 43 N TRPP (Polycystin), 43 NAADP, see Nicotine acid adenine TRPV (Vanilloid), 43 dinucleotide phosphate pharmacological attributes, 42 (NAADP) as polymodal sensors, 43 NAADP+, see Nicotinic acid adenine role and emphasis, 42 dinucleotide phosphate as therapeutic agents, 42 (NAADP+) TRPA1, 66–71 Na+/Ca2+ exchange-1, 742 α, β-unsaturated aldehyde, 69 Na+/Ca2+ exchanger (NCX), 709 alkylamides, 69 Na-Cl cotransporter (NCC), 282f, 561 cannabinoids, 69 N-acyldopamines,48t, 990 endogenous ligands, 70–71 N-acylsalsolinols, 646 isothiocyanates, 66 N-acyltaurine (NAT), 54, 61, 646 methyl salicylate, 70 NAD, see Nicotinamide adenine dinucleotide monoterpenoids, 70 (NAD) nicotine, 70 β-NAD+, 538, 817–818 thiosulfinates, 66–68 NADA, see N-arachidonoyl-dopamine vanilloids, 70 (NADA) TRPC and TRPP channels, 72t Naematoloma sublateritium (fasciculol), 52 TRPC1–TRPC6, 71 Nagasawa, M., 558 TRP family, 43 Nagata, K., 868 TRPM8, 62–65 Na+/H+ exchanger (NHE) regulating factor 2 endogenous ligands, 62–65 (NHERF2), 258, 506, 561–562 menthol receptor, 62 Nakao, A., 373–383 monoterpenoids, 62 N-(3-aminopropyl)-2-([(3- prostate, expression in, 62 methylphenyl)methyl]oxy)-N- TRPM1–TRPM7, 65 (2-thienylmethyl)benzamide TRPM1–TRPM8, 63t–64t hydrochloride salt (AMTB), TRPP2, 71–73 194–195, 711t TRPV1, 4355, 45t–49t, 67t–68t N-arachidonolylserine, 646 α, β-unsaturated dialdehyde, 51–52 N-arachidonoyl-dopamine (NADA), 48t, 54, brain structures, 44 190, 485, 646, 997 cannabinoids, 53 N-arachidonoylsalsolinol, 54 compounds, affinities, 52 N-arachidonylethanolamine (AEA, endogenous ligands, 54 anandamide), 646 functional vanillyl group, 44 Nasonov, D., 461 ginsenosides, 53 Nasturtium seeds, 66 identification, 43 Na, T., 263 immunoreactivity or mRNA, 44 NAT, see N-acyltaurine (NAT) miscellaneous compounds, 55 Natural product ligands nociceptive or pain sensing neurons, deorphanisation, 42 characterization, 44 diverse function toxins and peptides, 53–54 growth cone morphology, modification, triprenyl phenols, 52–53 43 vanilloids, 44–51 Index 1061

TRPV2, 56–58 non-speciﬁc Ca2+ sensitive cationic cannabinoids, 56 current (CAN Current), endogenous ligands, 56–58 596–598 probenecid, 56 TRP and diseases epilepsy TRPV3, 59–60 CAN/TRPC 4 and 5 currents, activated, dermatitis, 59 603, 605f endogenous ligands, 60 experimental models, 603 2+ hair growth, 59 TRPC and Ca channels 2+ monoterpenoids and diterpenoids, intracellular Ca levels, 601 2+ 59–60 L-type Ca channel blocker thermal nociception, 59 nifedipine, 601 thermoregulation, 59 TRPC and DAG vanilloids, 60 application of OAG, 602 TRPV4, 60–61 DHPG, 602 diterpenoids, 61 TRPC and IP3 endogenous ligands, 61 medial entorhinal cortex layer V cells, phorbol esters, binding site formation, 601 61 thapsigargin/cyclopiazonic acid, application, 601 TRPV2–TRPV6, 57t–58t TRPC and PIP2 use, 42 inhibits TRPC 4/5, 600 Nau, C., 498 role in “plateau” depolarization, 600 Nauli, S. M., 296, 772 TRPC channels and G-protein mediated Navarro-López, J. D., 595–606 receptors NBD, see Nucleotide binding domain (NBD) G-protein inhibitor GDP-β-S, 599 N-[4-3,5-bis(triﬂuromethyl)pyrazol-1-yl]- G-protein nonhydrolyzable activator 4-methyl-1,2,3-thiadiazole- GTP-γ-S, 599 5-carboxamine (BTP2), 157, TRPC channels and PLC 161 ET-18-OCH3, 600 NCC, see Na-Cl cotransporter (NCC) TRPC–NHERF interaction, 600 N β -dodecyl- -D-maltoside (DDM), 6, 29 U73122, 600 Negatively charged glutamate, 153 TRP channels and CAN current Neher, E., 107 mediators, 598 Nematodes M1 muscarinic receptors, involvement, Brugia malayi, 363 599 Meloidogyne incognita (plant parasite), (S)-3,5-dihydroxyphenylglycine effect, 363 occlusion, 599 “model worm,” C. elegans, 363 TRPC pharmacology or roundworms, 363 2-APB, 603 TRP channels/C. elegans, comparison, carbachol induced current, blockage, 364t–365t 603 T. spiralis and M. incognita genomes, 363, FFA application, 602 364t, 365 heteromers activated, 603 Nemes, Z., 849 SKF-96365, 603 Nephron and the collecting duct (CD), 277 TRP/pain processing/persistent activity Bowman’s capsule, 278 nociceptors, 604 glomerulus, 277 “plateau” potentials, 604 renal tubular system, 278 wind–up, 604 Nerve growth factor (NGF), 500, 548t, 550, Neural stem cell (NSC), 576–577 617, 640, 864, 971, 977 Neuregulin 1 (NRG1), 994 Netrin-1, 343–344, 988 NeurogesX, 647 Neural persistent activity (neuro)melanin-containing dopaminergic mechanisms neuron, 141 1062 Index

Neuromuscular disorders 793, 854, 856, 864, 891, 954, 4αPDD agonist, 1017 973 congenital spinal muscular atrophy, 1016 Nitro-oleic acid, 49t, 54, 71 HMSN2C, 1016–1017 NMB-1, see Noxious mechanosensation melastatin TRP, 1017 blocker-1 (NMB-1) R315W/R316C/R269H mutation, 1017 N-methyl-D-aspartate (NMDA), 999 SPSMA, 1016 receptors, 991 Neuronal calcium sensor-1 (NCS-1), 996 N-methyl-D-glucamine, 176, 733 Neuronal cell death, 382, 563, 998 NMR, see Nuclear magnetic resonance (NMR) Neuronal nitric oxide synthase (nNOS), 179 NMR spectroscopy, 3, 5–7 Neurotoxins nNOS, see Neuronal nitric oxide synthase 1-methyl, 4-phenyl pyridinium ion (nNOS) (MPP+/MPTP), 585 NO, see Nitric oxide (NO) Neurotoxin shellfish poisoning, 54 Noben-Trauth, K., 229–236 Neutral glutamine, 153 NO-cGMP-protein kinase G signaling Neutralization, 99, 479, 484, 498, 520, 643, pathway, 771 822–823 Nociception, 59–60, 96, 197, 367t, 457, Neutrophil, 90, 95, 381f, 532, 538, 769, 885, 493–495, 504, 582–583, 615, 890–891, 975 617–618, 620, 624, 625–629, Newson, P., 999–1000 785, 862, 866, 998 NFAT, see Nuclear factor of activated T cell Nociceptive reflex, 195 (NFAT) Nociceptors, 44, 115, 197, 492, 494, 496f, 497, N-formyl-Lmethionyl-L-leucyl-L- 503–504, 506–507, 509, 604, phenylalanine (fMLP), 90, 615–618, 620f, 621–627, 646, 548t, 558 790, 862–863, 868, 973–974, NGD-8243/MK-2295, 650t 976–977 NGF, see Bradykinin (BK); Nerve growth N-octyl-β-D-glucoside (OG), 6 factor (NGF) Node of Ranvier, 484 N-glycosylation sites N-oleoyl-dopamine, 54, 790 Asn-821, 186 N-oleoylethanolamine (OLEA), 646 Asn-934, 186 No Mechano Potential Channel C (NOMPC), NHERF-1, 551, 561 345 NHERF2, see Na+/H+ exchanger (NHE) Nongenomic effect of suckling, 248 regulating factor 2 (NHERF2) Nonionic and zwitterionic detergents, 6 Niacin (nicotinic acid), 999 See also individual entries Nickel-chelate affinity chromatography, 29 Nonmuscle myosin IIA, 177 Nicotiana tabacum (nicotine), 49, 55, 70 Nonmuscle myosin IIB, 177 Nicotinamide adenine dinucleotide (NAD), 65, Nonmuscle myosin IIC, 177 113, 380, 535, 538, 711t, 713, Non-selective cation channels (NSCC), 708 + + 769, 789, 817–818 Ca2 influx and Na influx, 709 Nicotine, 49t, 55, 70, 325, 332, 364t, 380, 973 “classical “ TRP (TRPC), 709 Nicotine acid adenine dinucleotide phosphate functional classes of, 709 (NAADP), 380, 538, 676, 816, CA channels, 709 818–819 constitutively active (CA) channels, 709 Nicotinic acid adenine dinucleotide phosphate ROC and SOC, 709 (NAADP+), 538 SAC channels, 709 Nielsen, D., 120 stretch activated (SAC) channels, 709 Nifedipine, 97, 601, 738, 821, 913 Gq/11/phospholipase C (PLC) coupling, Night blindness, 27, 73, 140, 1017–1019 709 Nikrozi, Z., 285 Na+/Ca2+ exchanger (NCX), 709 Nilius, B., 461, 463, NCX, 709 Nitric oxide (NO), 49t, 71, 179, 377, 532, 627, PLC coupling, 709 641, 669, 709, 719, 764, 774t, for vascular smooth muscle function, 709 Index 1063

vascular smooth muscle responsiveness, Nucleoside diphosphate-linked moiety X-type 709 motif 9 homology (NUDT9-H), Non-selective cation current (ICaNS), 128–129, 9, 380, 534–535, 547f, 817 137, 437, 814, 816, 824, 974, Nucleotid-associated proteins, 456 977 Nucleotide binding domain (NBD), 151, Nonselective cation current (NSCC), 708–709, 814 713, 717, 736, 738–739, Nudix box, 789 741–742, 814 NUDT9-H, see Nucleoside diphosphate-linked Non-selective cationic channels (NSCCa), 148 moiety X-type motif 9 homology presence, 148 (NUDT9-H) Non-TRPM8 mechanism, 198 NudT9-H domain, 9, 380, 534, 535f, 817 Noradrenaline, 397, 991 Numazaki, M., 500 NYX gene, 141 Norepinephrine, 669 NorpA gene, 395 Northern blot analyses, 243 O OAADPr, see 2-Oacetyl-ADP-ribose NO sensor, 377, 463, 533, 540, 713 (OAADPr) Novel therapeutic strategy, 787 2 -Oacetyl-ADP-ribose (OAADPr), 380 Nowycky, M. C., 580 OAG, see 1-Oleoyl-2-acetyl-sn-glycerol Noxious mechanosensation blocker-1 (OAG) effect (NMB-1), 71 OAG-induced TRPC6 channel activity, 399 N-(p-amylcinnamoyl)anthranilic acid (ACA), Oak ridge polycystic kidney (orpk) mouse, 65, 88, 89f, 94–95, 190, 711t, 291 819 Oancea, E., 135–143, 180 NPS R-467 (calcimimetic compound), 246 Obara, T., 348 NSC, see Neural stem cell (NSC) Oberacker, T., 566 NSCCa, see Non-selective cationic channels Oberegelsbacher, C., 566 (NSCCa) OASF (Orai-activating small fragment), 421t, NSCC blockers 421 Cd2+, 736 Ocimum gratissimum, 45t, 50 Gd3+, 736 Oesophageal reﬂux disease, 640t, 652t, 656 + β La3 , 736 OG, see N-octyl- -D-glucoside (OG) Ni2+, 736 25(OH)D, see 25-Hydroxyvitamin D SKF-96365, 736 (25(OH)D) Ohm’s Law, 476 N-terminal and truncated transmembrane Oh, S. B., 615–629 domains (TRPM2-S), 534, 1-Oleoyl-2-acetyl-sn-glycerol (OAG) effect, 536–538, 770, 817, 820 564, 894, 912 14 N-terminal ankyrin, 782 Oleoylethanolamide, 54 N-terminal extracellular ligand binding, 88 Olfaction, 108, 127, 129, 240, 831 N-terminal (TRPM1), 534 Olfactory adaptation, 240 N-(4-tertiarybutylphenyl)-4-(3-chloropyridin- Olfactory marker protein (OMP), 344 2-yl)tetrahydropyrazine- Olfactory sensory neurons (OSNs) 1(2H)-carboxamide (BCTC), ciliated OSNs, 344 188 cyclic nucleotide-gated channel A2 N-(4-tertiary-carboxamide (SR141716A), subunit, 344 188–191 OMP, 344 Nuclear factor kappa-B, 764 OR-type odorant receptors, 344 Nuclear factor of activated T cell (NFAT), 160, microvillous OSNs, 344 374, 375f, 376–377 TRPC2, 344 transcription factors, 1013 V2R-type receptors, 344 Nuclear magnetic resonance (NMR), 1, 3, 4t, ON bipolar cell, 138, 140–141, 1018 5–7, 10–19, 34, 344 On-cell patch clamp, 128 1064 Index

Oncogenic TRP channels, 929–940 PACSIN proteins, 549t, 559 cancer cell genotypes characterization, 930 PAEC, see Porcine aortic endothelial cells role in cancer development and progression, (PAEC) 930–939 Painful bladder syndrome, 97, 201, 867, 871 TRPC channels and cancer, 931–933 Pain upon inspiration, 970 TRPM channels and cancer, 937–939 Pajonk, F. G., 995 TRPV channels and cancer, 933–927 Palmer, C., 315–320 Ong, H. L., 435–445, 824 Panax ginseng, 47t, 53 ON pathway, 140 Pancreatic β-cell, 65, 160, 382, 716 On-target effect, 201 β-Pancreatic cell, 157 Open channel block mechanism, 395–396 β-Pancreatic cell line, 158 Oppenheimer, C. H., 454 Pani, Dr. B., 587 Orai1, 160, 404 Piggott, B., 333 + Ca2 selective ion channel, 420 PAP, see Phosphatidic acid phosphatase (PAP) functional domains of, 420t Paracellular pathway, 249, 251, 259–260, 766 Orai2 and Orai3, structure of, 420 Para-cellular transport mechanism, 88 Orai1 currents, 420 6-Paradol, 45t, 51, 70 Orai protein, 393, 417–420, 425, 440, 783, 888 Parasites, TRP channels in, 359–367 Orai1 (SOC protein), 376, 393 ectoparasites, 366–368 Orio, P., 517–528 endoparasites Organic blocker helminths, 363–366 clotrimazole, 88 protozoa,2–363 LOE908, 88 parasites infecting humans, 360t SKF-96365, 88 Parathyroid hormone (PTH), 246–248, 250t, Origanum vulgare (carvacrol), 57t, 59, 65 251, 258, 278, 283, 559, 917 Ornithoctonus huwena (Chinese bird spider), Parkinsonian syndrome, 585 48t, 53 Parkinsonism-dementia, 537 Orphaned TRP channel, 65 Parkinson’s disease, 141 Osmolarity-sensitive channel, 60 PARP, see Poly (ADPR) polymerase (PARP) Osmo-sensor, 463 Patch-clamp electrophysiology, 50 Osmotic cell swelling, 71 Patch-clamp technique, 162, 315, 789 Osmotic membrane stretch, 71 Patchliner (Nanion), 108–109, 112 OSM-9 protein, 240–241, 325–326, 328–330, PatchXpress (MDC), 108–110, 118, 122 330, 364t Patel, V., 1023 Osteoarthritis, 621, 640t, 651, 652t, 653–654 Pathological cardiac hypertrophy, 376 Otsuguro, K., 402 Pathophysiological functions TRPV channels Oval cells, 669, 669 in cancers, 951t Ovarian cancer (OC), 936 Paulsen, I. M. S., 285 Over-expression system, 298, 394 Pausinystalia yohimbe (yohimbine), 55 Oxaliplatin (chemotherapy drug), 197 PBC, see Pre-Bötzinger complex (PBC) Oxidation, 96, 532, 539, 770, 774t PBP (polycystic breakpoint), 1027 Oxidative stress, 112–113, 379–380, 382, p-bromophenacyl bromide (BPB), 94 457, 531–540, 585–586, 717, PC-3 cell, 200 769–770, 789, 795, 820, 971 PC-12 cell, 90, 582 4-Oxononenal (4-ONE), 972 PC3 (prostate cancer) cells, 954, 955 Oxygenated eicosatetraenoic acids, 646 PDBu, 404, 602 OxyR (transcriptional regulator protein), 457 4α-PDD, see 4α-Phorbol 12,13-didecanoate (4α-PDD) P 4αPDD agonist, 14, 1017 P53, 140, 951, 960 Pedretti, A., 480 PA, see Phosphatidic acid (PA) Pendred syndrome, 253 Pacemaker HCN channel, 162 Peng, J.-B., 239–263 Paclitaxel, 628 Penicillium brevicompactum, 71, 72t Index 1065

Penna, A., 558 4-β-Phorbol 12-myristate 13-acetate (PMA), Peptidyl-prolyl isomerase (PPIase), 344 61, 499, 627, 822 Perforated patch technique, 175 Phosphatidic acid (PA), 395, 396f, 715 Periaqueductal grey (PAG), 990, 992, 996 Phosphatidic acid phosphatase (PAP), 395–396 Peripheral demyelination model, 626 Phosphatidylinositide, 99 Peripheral neuropathic pain, 640t Phosphatidylinositide 3 kinase (PI(3) kinase), Periplaneta Americana (cockroach), 93 550 Permeability of ion (Pion), 128 Phosphatidylinositol 4,5-bisphosphate, 130, P-glycoprotein (MDR1), 29, 50 159, 177, 188, 244, 377, 396f, PH, see Pleckstrin homology (PH) 416, 495, 600, 643, 709, 783, PHA II, see Pseudohypoaldosteronism type II 787f, 815, 834 (PHA II) Phosphatidylinositol bisphosphate (PIP2), 2, Pharmacology and druggability 43, 90, 91f, 151, 154–156, 161, agonists 163, 177, 188, 244, 327–328, biogenic amines, 646 330, 378, 393, 395–404, 416, resiniferatoxin (RTX), 646 436, 436–437, 464, 475, 495, 501–503, 525, 550, 574f, 600, antagonists 602, 617, 624, 638f, 643, 709, Aminoquinazolines, 647 711f, 712–715, 787f, 815–816, Biaryl carboxamides, 647 824, 834–836 dye ruthenium red, 647 Phosphatidylinositol 3,5-bisphosphate 4-ﬂuopyridine amides, 647 (PI(3,5)P2), 258, 332 non-vanilloid compounds, 647 Phosphatidylinositol 4,5-bisphosphate (PIP2), Phenylchromones, 647 130, 154, 177, 188, 244, 377, Piperazinyl benzimidazoles, 647 396f, 416, 495, 600, 643, 709, Piperazinyl pyrimidines, 647 783f–784f, 815, 834–835 pore blocker, 647 Phosphatidylinositol-3,4 kinase (PI3,4 K), 56 Pyridoindazolones, 647 Phosphatidylinositol-3-phosphate-5-kinase spiroisoxazolopyridine amides, 647 PIKfyve (PIP5K3), 258 vanilloid derived, 647 Phosphine oxide Pharmaco-mechanical coupling, 708 derivative Phase I clinical trial WS-148, 188 D-3263, 188, 200–201 Phosphofurin acidic cluster sorting proteins 9-Phenanthrol, 63t, 65, 153f, 157 PACS-1, 559 Phencyclidine (PCP), 995 PACS-2, 564 Phenylalanine, 35, 551 Phosphofurin acidic cluster sorting proteins 1 Phenylchromones, 647 and 2 (PACS-2 and PACS-1), Pheromone-evoked spiking, 128 295 4α-Phorbol 12,13-didecanoate (4α-PDD), 14, Phosphoinositide-4,5-bisphosphate (PIP2), 2 58t, 61, 90, 95, 118, 186, 549, Phosphoinositide 3-kinase (PI3-kinase), 294, 627–628, 674, 690, 755, 767, 617, 735f 771, 774, 792, 794, 797, 822, Phosphoinositide-speciﬁc phospholipase C 863t, 869, 957, 978, 1017 (PI-PLC), 396f, 814, 818, 824 Phorbol ester, 61 Phospholipase A2 (PLA2), 93, 532 binding site formation at TRPV4, 61 activity, 65 S556, 61 signaling pathway, 188 Y555, 61 Phospholipase C (PLC), 88, 99, 112, 128, 327, TRPV4, activation residues, 61 373, 956 L584, 61 members, interaction, 177 W586, 61 PLC-β1, 177 Phorbol esters 4-alpha-phorbol 12,13- PLC-β2, 177 didecanoate (4α-PDD), PLC-β3, 177 627 PLC-γ1, 177 1066 Index

Phospholipase C (PLC) activity, 88, 112, 126, PKD2L2, 292, 299, 691, 891, 919, 1023 177, 188, 327, 373, 417, 503, PKD1L3/PKD2L1 TRPP channels, 836–840 554, 586, 624 ASIC channels, 837 Phospholipases, 532 DTA, 837 Photoaffinity labeling experiment, 96, 377 HEK 293T cells, 837 Photoreceptor cells, 342, 533, 554, 732 functional properties, 837 Physialia physalis (bluebottle or Portugese PKD1L3/PKD2L1 heterodimer, 838 Man O’ War), 54 peripheral taste system, 837 Physiological mechanism, 188, 695 sour receptor in taste system, identification Pichia pastoris (P. pastoris), 6, 28 of, 836 PIGEA-14, 295 stimulated by sour tastants, 838f PI3,4 K, see Phosphatidylinositol-3,4 kinase PKD1L1 (Polycystic kidney disease 1 like 1), (PI3,4 K) 301–302 Pike, J. W., 246 Dot-blot analysis and RT-PCR studies, 301 PI(3) kinase, see Phosphatidylinositide 3 in testis’s Leydig cells, 301 kinase (PI(3) kinase) Pkd1l1−/− mice, 301 PI-3-kinase, 400–401, 404, 557 primary cilia dyskinesia, 301 PI-4-kinase, 399 protein architecture of, 301 PI-5-kinase, 399 PKD1L2 (Polycystic kidney disease 1 like 2), Pion, see permeability of ion (Pion) 301 PIP2, see Phosphatidylinositol bisphosphate Dot-blot analysis and RT-PCR studies, 302 ostes/ostes (PIP2); Phosphatidylinositol homozygous mice, 302 4,5-bisphosphate (PIP2) Polycystin-1 PKDREJ subfamily, 302 PI(3,5)P2, see Phosphatidylinositol PKD2 (polycystin-2) gene, 919 3,5-bisphosphate (PI(3,5)P2) PKDREJ, 300–301 Piperaceae, 50 homology of, 300 Piperazinyl benzimidazoles, 647 for mammalian sperm, 300–301 Piperazinyl pyrimidines, 647 northern blot analysis and RT-PCR studies, Piperine, 45t, 50, 493 300 Piper nigrum (black pepper), 45t, 50 sea urchin receptor for egg jelly (suREJ3), PIP5K3, see Phosphatidylinositol-3- 300 phosphate-5-kinase PIKfyve PLA2, see Phospholipase A2 (PLA2) (PIP5K3) Placenta, 148, 251–252, 294, 556, 909–921, Pirenzepine, 599 933 PKA, see Protein kinase A (PKA) Planar substrate, 108 PKA-regulated entry mechanism, 131 Planells-Cases, R., 491–509 PKB, see Protein kinase B (PKB) Plant thermosensory perception, 456 PKC, see Protein kinase C (PKC) Plasma membrane channel PKCβ, see Protein kinase Cβ (PKCβ) Orai1 (CRACM1), 92 PKC(δ), 557 Orai2 (CRACM2), 92 PKC-dependent mechanism, 394, 402, 404 Orai3 (CRACM3), 92 PKC-independent mechanism, 394, 398, Platelet activating factor (PAF), 890, 975 401–402 Platelet-derived growth factor, 178, 768, 954 PKC phosphorylation, 246, 497, 499, 560, 815 PLC, see Phospholipase C (PLC) activity PKD1, 16–17, 71 PLCγ2-deficient cell, 374 knockout mice, 73 PLC-signaling cascade, 158 attenuated cyst formation, 73 Pleckstrin homology (PH), 374 PKD-1, 564, 919–920 PMA, see 4-β-Phorbol 12-myristate 13-acetate PKD2, 289–290, 293–294, 302, 319, 327, (PMA) 672t, 61, 885, 891–892, 919, PMA1 promoter, 29 921, 1023–1025 P/n leak subtraction, 113 PKD2L1, 292, 297–298, 691, 833, 836–838, Pocock, 767 841, 891, 919, 1023 Polcystic kidney disease, 797 Index 1067

Poly(ADPR) glycohydrolase, 380 Polymodal sensor of noxious irritants, 972–973 Poly (ADPR) polymerase (PARP), 534 Polyunsaturated fatty acid (PUFA), 63t–64t, Polyamine, 44, 55, 63t, 156, 483, 646, 711t 328, 395–396 Polybasic tail, 439, 441 Polyvalent cations, 642 Polycystic kidney disease, 17, 71–73, 88, Pons, 584 289–293, 298–303, 318–319, Poo, M. M., 343 348, 564, 691, 771, 785, 789, Porcine airway SM tissues, 732 836–838, 891–892, 919, 1023 Porcine aortic endothelial cells (PAEC), 586, Polycystic kidney disease-1-like 3 (PKD1L3) 769, 795 TRPP channels, 836–838 Pore turret, 478, 525, 525f Polycystic kidney disease-2-like 1(PKD2L1) Pore widening, 484–485 TRPP channels, 846–838 Positional cloning approach, 232 Polycystic kidney disease (PKD), 17, 27, Positron emission tomography (PET), 991 71–73, 88, 289–293, 297–303, Postherpetic neuralgia, 198, 621, 647, 652f 318–319, 348–349, 564, 691, Potassium channel, 28 771, 785, 789, 836–838, BK, 109 891–892, 919, 1023 KCNQ4, 109 Polycystin-1, 71–72, 288f, 289, 292–293, Potent defensemechanism, 98 300–303, 348–349, 892, 1023, Praetorius, J., 277–285, 296 1025 Pre-Bötzinger complex (PBC), 159f, 161 Polycystin 2, 71, 292, 348–349, 691, 891–892, Pregnant human myometrial smooth muscle 919, 1023 cells (PMH1), 698–693 Polycystin group (TRPP), 88 Pregnenolone, 63t, 65, 90, 92f, 95, 96f, 114, Polycystin-1 (PC-1), 292–293 690, 820, 821f, 975 features of, 293 Pregnenolone sulphate, 63t, 65, 90, 92f, 95, GPS, 293 96f, 114, 690, 820, 821f LH2/PLAT domain, 293 Premolten globule, 459 REJ domain, 293 Prenatal lethality, 178, 922 mutations in PKD1, 292–293 Pressure overload-induced cardiac hypertrophy, PC-1 and PKD1L1, 293 96, 787 PKD1-like genes, 293 Prevarskaya, N., 929–940 PKD1L1, 293 Prevarskaya’s team, 934 PKD1L2, 293 Primary thermosensory events in cells PKD1L3, 293 CSP-induced change mechanisms, 452 PKDREJ (PC-REJ), 293 DNA thermotropic reactions, 455–456 PKDREJ-like proteins genomic thermo-sensitivity, 456 PKDREJ/PKD1L2/PKD1L3, 293 oligonucleotide duplexes, 456 receptor or adhesion molecule, 293 pLO88 plasmid, 456 TRPP1 encoded by PKD1 gene, 292 transitions, 456 Polycystin-2 (PC 2), 292, 348, 602, 883t, 892, “twisted” superhelical conformation, 919, 1023 455 Polycystin TRPs, 1023 membrane lipids ﬂuidity, 454–455 adult polycystic kidney disease (ADPKD), thermometers, role, 454 1023 protein thermometers, 456–458 PKD1, PBP (polycystic breakpoint), 1023 OxyR activation, 457 TRPP1 (or PKD2), 1023 phase transitions, 458 TRPP2 (PKD2L1 or PKD2-like 1), 1023 structural transitions, 458 TRPP3 (PKD2L2 or PKD2-like 2), 1023 thermal sensitivity, characterization, Polygonum hydropiper (polygodial), 46t, 52, 457 68 protein thermometers, structural features, Poly-L-lysine, 399, 402 462–464 Polymodal gating mechanism, 187 polymerization, 464 Polymodal receptors, 469–486 tertiary/quaternary structure, 463 1068 Index

Primary thermosensory events in cells (cont.) Prostaglandins, 68t, 70–71, 198, 497, 506, 557, thermotropic reactions, modulation, 623, 627, 641, 646, 669, 850, 464 854, 864–865, 913, 972 TRPV1 C-terminal domain, 463 Prostate-specific antigen (PSA), 938 protein thermosensitivity, biophysical Protein Data Bank, 6 aspects, 458–462 Protein 3D structure enthalpy end entropy changes, 460 determination methods free energy profile of globular protein, electron cryomicroscopy (cryo-EM), 5 hypothetical model, 459f NMR spectroscopy, 5 hypothesis of native aggregation, 462 X-ray crystallography, 5 natively unfolded proteins, 459 Protein expression, 7, 19, 29, 198, 283, 669, protein structural information 679f, 690, 694, 719, 740–741, conversion, strategies, 462f 751–752, 764, 768, 770, 794, RNA thermotropic reactions, 455–456 890, 910, 911t, 912, 916t, hybrid (intermolecular forms), 455 919t–920t, 935–936, 950, 952, regulatory elements, 455 954, 956, 958, 1014 secondary and tertiary structures, 455 Protein-free micelles, 33 thermometers operation, 455 Protein kinase A (PKA), 10, 11f, 130–131, temperature change, effects, 451–452 151, 186, 188, 212, 246–247, physico-chemical change, 452 378, 494f, 495, 496f, 497–498, temperature-induced conformational 499, 501, 503, 520, 536, 557, change, 452 563, 617, 624, 628, 643, 712, temperature-controlled process 711t, 815, 819, 893 Protein kinase B (PKB), 258, 649t, 954–955 cold-shock gene, expression, 452 Protein kinase Cβ (PKCβ), 375–376 heat-shock gene, expression, 452 Protein kinase C (PKC), 61, 158, 188, 246, temperature sensing biomolecules, 454 495, 554, 709, 883, 888 TRP subfamilies Protein kinases, 10, 61, 130, 154, 156, TRPA, 457 177–178, 186, 188, 246–247, TRPC, 457 258, 375, 378, 392, 477, TRPM, 457 494f, 495, 496f, 497, 499, TRPML, 457 501, 503–504, 532, 554, 557, TRPN, 457 562, 617, 643, 709, 712, 714, TRPP, 457 754–755, 771, 784, 787f, 788, TRPV, 457 822, 883, 886, 888, 960 PRKCSH, 677 Protein–ligand interaction, 2, 12 Pro-algesic effect, 51 Protein–protein interaction, 12, 16, 26, 381f, Prober, D. A., 346 416, 419t–420t, 423, 463, 883, Profibrotic TGF-β1 signal, 179–180 894 Progressive familial heart block, type 1B Proteins (TRP), TRPCs, 416–417 (PFHB1B), 1020 Ca2+:Na+ permeability ratios, 417 Pro-inflammatory agents canonical TRP (TRPC) subfamily, 416 histamine, 766 cytoplasmic N- and C-termini, 416 thrombin, 766 expression levels, 417 Proinflammatory bradykinin signaling, 179 siRNA or shRNA, 417 Proliferating Cell Nuclear Antigen (PCNA), in SOCE or ROCE, 417 934, 939, 959 subfamilies of TRP, 416 Proliferation, role of TRP in SMC, 697 TRPC1 (mammalian TRP protein), 416 chronic hypoxia, 697 trp mutant of Drosophila, 416 secondary and idiopathic PAH, 697 TRP signature motif (EWKFAR), 416 TRPC1 and TRPC3, 697 Proteomic approach, 382 TRPC6 upregulation, 697 Protozoa, 362–363 Prostaglandin E2 (PGE2), 198, 506, 627 apicomplexans (Plasmodium species), 362 Index 1069

Cryptosporidium parva protein, 362 Putrescine, 55, 483, 646 kinetoplastids, 362 Pyrazole compound (Pyr3), 89f, 96–97, 375f, metamonads, 362 376–377, 787f, 787 mosquito or biting fly, 362 Pyr3 compound, 96–97 TRP-like channels, 362 Pyr3-derivative, 96 TRPML-like genes, 362 Pyridoindazolones, 647 lmmlA (LmjF07.0910), 362 Pyridyl piperazine carboxamides, 648t lmmlB (LmjF26.0990), 362 TrTrypDB, 362 Q Proximal tubule (PT), 259, 278 Q977E substitution, 153 Psalmopoeus cambridgei, 53 Qin, F., 491–509 VaTx1, 53 Qin, N., 185–201 VaTx2, 53 Qiu, A., 242 VaTx3, 53 QPatch HTX multi-hole system, 109, 111 P53 Ser15, 951 QPatch (Sophion), 108–111, 111f, 113f, Pseudohypoaldosteronism type II (PHA II), 115–116, 118, 119, 120, 645 254, 255t, 256 qRT-PCR, see Quantitative reverse- Pseudohypoaldosteronism type I (PHA 1), 278 transcription PCR (qRT-PCR) 18–25 pS single channel conductance, 153 Q10 (temperature coefficient), 380, 457–458, Psychiatric disorders, 987–988, 1000 473, 475–477, 479, 483, 521, 642, 819 depression and anxiety, 990–991 Quantitative reverse-transcription PCR TRPC channels, 991–992 (qRT-PCR), 138 TRPV channels, 992–993 Quinazolinon analogue, 649t schizophrenia, 994–995 QutenzaTM, 647 TRPC channels and, 995–996 QX314, 622 TRPV channels and, 996–997 TRP channels in brain R TRPC channels, 988–989 Rab9, 549t, 553 TRPV channels, 989–990 Rab11, 549t, 553, 561 PTH, see Parathyroid hormone (PTH) RACK1, see Receptors for activated PT pore, activation, 532 C-kinase-1 (RACK1) PubMed, 97 Rapid inspiration, 641 Puertollano, R., 236, 1025 Rauwolfia, 55 PUFA, see Polyunsaturated fatty acid (PUFA) RBL-2H3mast cell line, 178 Pufferfish (Fugu rubripes), 351 R269C mutation, 14, 1015t, 1017 Pulmonary arterial smooth muscle cells R316C mutation, 14, 1015t, 1017 (PASMC), 422, 690–691, R59949 (DAG kinase), 395, 396f, 398, 401 695–696, 796, 799 rdgA gene, 395 Pulmonary artery hyperreactivity, 696–697 Reactive nitrogen species (RNS), 179, 532, CH-PAH in rats, 696 534, 676 chronic hypoxia-induced PAH (CH-PAH), Reactive oxygen species (ROS), 178, 352, in rats with, 696 380–381, 532–533, 539–540, model of normobaric CH-PAH rats, 696 586, 669, 675–676, 695, 717, primary hypertension (idiopathic PAH), 766–767, 769, 773f, 818–819, 696 886, 920, 935, 954 + resting [Ca2 ]i, 696 Reale, V., 817 siRNA or antisense oligonucleotides, 696 Reaves, B. J., 359–367 studies in rat and in TRPV4 –/– mice, 696 Reboreda, A., 595–606 Pulmonary hypertension, 782 Receptor for egg jelly (REJ) domain, 293, Pulmonary hypertension and TRP, 695–696 300–301, 892 pulmonary arterial hypertension (PAH), Receptor-mediated mechanism, 130 695 Receptor-operated Ca2+ entry (ROCE), 328, Purinergic P2X receptor, 50 415, 424f, 739, 742 1070 Index

Receptor operated cation entry (ROCE), 783 TRPV1, 914–915 Receptor-operated channel (ROC), 328, 393, TRPV2/TRPV3, 915 688, 708 TRPV4, 915–917 Receptors for activated C-kinase-1 (RACK1), TRPV5/6, 917–918 376, 423, 888 Research toolkits, TRPV1 Receptor signaling integration clinical status TRPC3, 374–377 anesiva has Adlea in phase-III, 651 + DAG-activated Ca2 influx role, clinical trials beyond phase-I, 652t proposed model, 375f Merck–Neurogen alignment on partial PH-like domain, 374–375 MK-2295, 653 pathophysiological process, 376 neurogesx has QutenzaTM in phase-III, SOC encoding, 374 647–650 TRPC5, 377–379 Winston Laboratories has Civamide in activation proteins and factors, 377 phase-III, 651–654 covalent modifications, 377 electrophysiology endothelial cell layer, distribution, 378 automated patch clamp techniques, 645 feedback cycle, proposed model, 379f IonWorks, 645 labeling and functional assay, 377 manual patch clamp recording, 645 in neurite extension, 378 QPatch system, 645 TRPM2, 379–382 florescence imaging and 45Ca2+ flux downstream signaling cascades, 381 assays electrophysiological data, 380 45Ca2+ based assays, 646 on H2O2-induced chemokine FLIPR platform, 646 production in monocytes and production and purification, current macrophages, 381f methods H2O2-induced TRPM2 activation, 380 fermentation, 644 insulin secretion, 382 insect cells, 644 + NAD metabolites, 380 mammalian cells, 644 oxidative stress, activation, 379 S. cerevisiae yeast strain BJ5457, 644 sustained ion influx, maintenance, 382 yeast, 644 tyrosine phosphorylation, 380 radio ligand binding assays Receptor tyrosine kinase (RTK), 43, 327, 535, 3H-A-778317 (Abbott Laboratories), 574f, 576–587, 888–889, 1012 645 Recombination gene activator (RGA), 507, 3H-Resiniferatoxin (PerkinElmer Life 549, 559 Sciences), 644–646 Rectal pain, 621 Kd and Bmax, 644 Redox sensor, 88, 94, 113, 150, 795 Resiniferatoxin (RTX), 44, 45t, 50–53, 55, 98, Refilling mechanism, 90 190, 191t, 481, 485, 493, 499, Regulator of Gprotein signaling (RGS), 331, 527, 620–621, 644, 646, 674, 994 863t, 866, 989, 952, 989, 996 Renal outer medullary potassium (ROMK), Respiratory sensory irritation, 973 247 Respiratory symptoms and pathophysiology, Reperfusion injury, 532, 537–538, 676, 790 969–970 Reproductive (female) organs and placenta, sensory neuronal TRP channels as initiators TRP channels in, 909–922 and regulators, 970 mammary glands, 921 TRPA1, 972–973 TRPC family, 911–914 TRPM8, 975–976 TRPM family, 919 TRPV1, 971–972 TRPP family, 919–921 TRP channels in airway cells of TRP proteins in non-neuronal origin, 974 female reproductive organs, 911f airway structural and immune cells, human placenta, 914f 975–976 TRPV family, 914–918 capsaicin receptor and, 976–978 Index 1071

intracellular calcium homeostasis and TRPV3 and TRPV4 inflammation, 975 activated by hypo-osmotic conditions, TRPA1, 974–975 627 Reverse transcription–PCR, 957f acute inflammatory mechanical Reynaud’s phenomenon, 723 hyperalgesia development, 628 RGA, see Recombination gene activator agonists, 627 (RGA) chemical ligands, 627 RGS-4, 994 inhibitor paclitaxel, 628 R154H, 261–262 prostaglandin E2 (PGE2) release, 627 Rhabdomyosarcomas, 939 TRPV4 in visceral nociception, 628 Rhaboid tumours, 939 Romanin, C., 421 RHC80267 (DAG lipase), 396f, 398 ROMK, see Renal outer medullary potassium Rheumatoid arthritis, 458, 640t (ROMK) R269H mutation, 14, 1015t, 1017 ROS, see Reactive oxygen species (ROS) Rhodopsin mutant, 28 Rosado, J. A., 413–426 “Riboswitches,” 455 Rosenbaum, T., 500 aptamer, 455 Rosenberg, P., 753 expression platform, 455 RPN1, zebrafish functions of, 345–346 Ricinoleic acid, 49f, 55 immunolocalization studies in Xenopus, RN-1734, 89, 98 345–346 RN-1747, 89f, 98 TRPN1 (NOMPC), 345 RNAi, see RNA interference (RNAi) Rs11078458, 949, 956 RNA interference (RNAi), 376, 536–537, 690, Rs65002729, 949, 956 913, 955 RT4 (urothelial cell line), 950, 952f, 956 RNS, see Reactive nitrogen species (RNS) RTK, see Receptor tyrosine kinase (RTK) ROC, see Receptor-operated channel (ROC) RT-PCR screening, 130 ROCE, see Receptor operated cation entry RTX, 952, see Resiniferatoxin (RTX) (ROCE) Ruthenium red, 69, 99, 110–111, 111f, 246, Rohon Beard primary sensory neurons, 348 251, 483, 643, 647, 695, 711t, Role in pain sensation 715, 771, 792, 794, 797, 848, perspectives 852, 856, 918, 978 thermal hyperalgesia, 628 Ruthenium red-sensitive vasorelaxation, 69 thermal nociception, 628 R315W mutation, 14, 1016 TRPA1 Rythmogenesis, 161 in cold pain and hyperalgesia, 624 Ryazanov, A. G., 351 induces heterologous desensitization of Rychkov, G. Y., 667–680 TRPV1, 625–626 in mechanical hyperalgesia, 625 S tissue damages, 623–624 S556, 61 TRPM8 SAC, see Stretch activated channels (SAC) analgesia in different pain models, 626 Saccharomyces cerevisiae (S. cerevisiae), 6, CFA injection, 626 28–30, 35 formalin-induced nocifensive behavior, SAG, see 1-Stearoyl-2-arachidonoyl-sn- 626 glycerol (SAG) receptor of menthol, 626 Sah, R., 173–180 TRPV1 Saito, S., 350 in central terminals of primary afferents Sakmann, B., 107 and CNS, 618–620 Salazar, H., 486 decreased arthritis-induced pain, 618 Saleh, S. N., 404 in deep tissue pain, 618 Salicylates, 49t, 55, 68t, 70 in heat pain and thermal hyperalgesia, Salido, G. M., 413–426 616–617 Salix, 49t, 55 therapeutic approaches, 620–623 Sallé, L., 147–165, 814 1072 Index

Sanders, K. M., 318 Ser20, 951 Sanofi-Aventis, 654 Ser502, 643–644 Santoni, G., 947–961 Ser800, 644 SAR-115740, 654 SERCA inhibitors, 393, 436, 673 Sarcoplasmic reticulum (SR), 317, 414, 688, SERCA pump, 436, 574f 693–694, 708, 720, 736, 753, SERCA (sarco/endoplasmic reticulum 799 Ca2+-ATPase), 414 Sato, Y., 345 Serine, 10, 50, 64t, 177, 245–246, 418, 419t, Savineau,J.P.,687–699 422, 457, 477, 538, 560, 564, SB-705498, 621, 648t, 651, 652f, 653–654 644, 693, 713, 786, 788, 893 SB-782443, 654 Serotonin, 72t, 326, 669, 797, 990–992, 995 SB-366791 (TRPV1 blocker), 98, 642, 649t, Ser392 phosphorylation, 951 655 SESTD1 (PI binding protein), 402 Scaffold protein caveolin-1, 764 Severe combined immune deficiency (SCID) Scalding, 98 syndrome, 415, 438 Scapuloperoneal spinal muscular atrophy Sf9 cell, 6, 98, 882 (SPSMA), 14, 61, 1015t, sh, see Short-hairpin (sh) 1016–1017 Shaker K+ channels, 5f, 519 SCCD, see Semicircular canal duct (SCCD) Sham-operated littermate, 129 S. cerevisiae Shawn Xu, X. Z., 323–333 TRP channels, 316–316 Shear force, 770, 772 channel gating, 316–317 Shigellae, 453 mammalian, 316 Shim, S., 343–344 patch-clamp surveys, 316 Shine–Dalgarno (SD) sequence, 455 yeast strain, 316 Shoeb, M., 881–895 yeast vacuolar channel (YVC), 316 6-Shogaol, 45t, 51, 70 TRPP2 homologs in, 319–320 Short-hairpin (sh), 138, 349 Schistosoma, 230, 360t, 365t SHR, see Spontaneously hypertensive rat Schizophrenia, 994–995 (SHR) TRPC channels and, 995–996 ShRNA, 126, 214, 226–227, 417 TRPV channels and, 996–1000 SH-SY5Y cells, 586, 931–932 Schrøder, R. L., 120 Scotopic vision, 140 Sickle-cell disease, 458 Sidi, S., 345 SD, see Shine–Dalgarno (SD) sequence 2+ SDS PAGE, 29 Signal-regulated Ca entry (SRCE), 913 Sea squirts (invertebrate chordates), 351 Sildenafil, 787f, 798–789 SeatleSNPs program, 260–261 Simard, C., 147–164, 814 Second law of thermodynamics, 460 Simon, P., 165 Sec63 proteins, 677 Simon, S. A., 501 Secretion coupling, 436, 812, 815–816 Singh, B. B., 552, 573–587 Selectivity filter, 5f, 34, 151, 420t, 470, 471f, Single channel analysis, 154 484, 486, 525f, 643 Single molecule photobleaching, 17 Selemon, L. D., 994 Single nucleotide polymorphisms (SNP), 136, Selvaraj, S., 573–587 179, 239–240, 494, 539, 947, Semicircular canal duct (SCCD), 252 998 Sensory ganglia, 346, 616, 626–627 Single particle cryo-EM, 7, 9, 30 Sensory neuronal TRP channels as initiators Single-particle electron microscopy, 33 and regulators, 970 Single-particle reconstruction method, 30, 32 TRPA1, 974–975 SiRNA inhibited cell proliferation, 178 TRPM8, 975–976 Sir2 protein deacetylase reaction, 380 TRPV1, 971–972 Six putative transmembrane segments (S1–S6), Sensory transduction process/mechanism, 2, 186, 324 451–452, 463 Skeletal disorders, 1014, 1016 Index 1073

Skeletal muscle, gene expres- TRPC, 689 sion/function/implications TRPM, 690–691 calcium entry pathways in sarcolemma TRPP, 691 ion channel blockers, inhibition, 750 TRPV, 689–690 Mn2+ quench technique, 750 physiological/pathophysiological roles of gene expression TRP and gastro intestinal tract, 697–698 detected in chick and mouse muscle TRP and uterine contractile activity, cultures, 751 698–699 flexor digitorum brevis isolated, 751 TRP and vascular system, 692 transcripts coding, 752 proliferation, 796 TRPV2 translocation, 752 relaxation cycle, TRP in, 692–694 implications for disease human TRPC1 gene in rat pulmonary cardiac-specific overexpression of artery, 692 TRPV2, 756 rat pulmonary arterial and aortic SMC, cytoskeletal scaffolding protein, 756 menthol in, 694 Duchenne muscular dystrophy, 755 rat skeletal muscle arterioles, capsaicin fibrosis, 755 in, 694 muscle damage, 755 ryanodine receptor (RYR), 693 muscular dystrophy in mdx mice, 756 SMC of TRPC1(–/–) mice, 693 necrosis of muscle fibres, 755 TRPC6, 693 progressive muscle weakness, 755 TRPC3 and TRPV4, 693 α-syntrophin and dystrophin, 755 “With No Lysine (K) Kinases” (WNK1 linking physiologically detected cation and WNK4), 693 channels, 750–751 SNAP-25, 556, 832 localization and function Snapin, 506–507, 549t, 553, 556, 563, 582–583 Ca2+ leak channel in sarcoplasmic Snapin – TRPC6 – α1A-adrenoceptor complex, reticulum, 753 553 glucose transporter GLUT4, 753 SNARE-mediated process, 212 interaction with triadic proteins, 753 SNARE proteins, 506, 556, 574f, 888 myopathy, 753 SNL, see Spinal nerve ligation (SNL) TRPC subfamily, 752–754 SNP rs1556314, 382 TRPM subfamily, 755 SOAR (STIM1 Orai-activating region), 419t, TRPV subfamily, 754–755 422–423 Skeletal muscle ryanodine receptor, 65 SOC, see store-operated Ca2+ channel (SOC); SKF-96365, 738 store operated channel (SOC) + action, 603 SOCE, see Store-operated calcium (Ca2 ) characterization entry (SOCE) ATP-stimulated cation current, 90 Solanaceae, 70 fMLP-stimulated cation current, 90 Somatosensory systems, 998–999 receptor-regulated isoform, 90 Sourjik, V., 462 discrimination S1P, see Sphingosine-1-phosphate (S1P) ATP-induced Ca2+ entry mechanism, Spearmint, 626 90 αII-Spectrin, 551 bradykinin-induced Ca2+ entry Spermatocyte, 129, 882, 886, 892 mechanism, 90 Sperm fertilization, 88 SK-Mel 19 melanoma cell, 142 Spermidine, 55, 483, 646 SMD, see Spondylometaphyseal dysplasia Spermine, 55, 63t, 65, 156–157, 483, 646, (SMD) 711t, 715 SMDK, see Spondylometaphyseal dysplasia Sphingolipid sphingosylphosphorylcholine, 65 Kozlowski type (SMDK) Sphingosine-1-phosphate (S1P), 581, 715, 797, Smooth muscle cells (SMC), TRP channels in, 820 687–699 Spinal nerve ligation (SNL), 198, 624 expression of Spiroisoxazolopyridine amides, 647 1074 Index

S. pombe, TRP homologs in, 318–319 FRET microscopy, 421 ADPKD, 348 lysine residues in BLAST analysis, 318 STIM1((684)KK(685)), pkd2 gene analysis, 319 421 TRPP2, 318 OASF (Orai-activating small fragment), Spondylometaphyseal dysplasia Kozlowski 421 type (SMDK), 14, 1015t, SOAR (STIM1 Orai-activating region), 1016–1017 421 Spondylometaphyseal dysplasia (SMD), 14, STIM1 and TRPC1, functional 61, 1015–1016 association, 422 Spongia ofﬁcinalis (isocopalendial), 47t, 52 STIM1 ERM domain, 422 Spontaneously hypertensive rat (SHR), 162, STIM1 K-domain, 422 179, 693, 719, 789, 798 complexes, calcium entry pathways, Spontaneous transient outwards currents 422–426, 424f (STOCs), 722 CRAC channels, 423 Sprouting and capillary tube formation, 768 in HEK-293 cells, 423 SPSMA, see Scapuloperoneal spinal muscular in human platelets, 425 atrophy (SPSMA) human platelets, expression of, 423 Sputum production, 970 lipid rafts, role of, 424–425 S4 (R842), 520 methyl-β-cyclodextrin (MBCD), use of, Src kinases, 503, 557, 563, 600, 605, 640, 643, 424 735t protein-protein interaction, 423 S4–S5 linker, 186, 381, 519–520 role of IP3 receptors, 422–423 Stable specialized ampliﬁer, 107 in sea urchin eggs, 422 Stadler, A., 461 SOC channel subunit, 425 Stadler,Dr.A.M.,461 in SOCE and ROCE, 425–426 Stajich, J. E., 260 St. John...wort, 97, 991 STAM-1/Hrs, 565 Stop-and-go liquid application, 109 Stamler, J. S., 378 Store-dependent channel, 444 Stark TRPM4 mRNA expression, 162 Store-dependent mechanism, 130, 394, 398 Starvation-induced apoptosis, 200 Store-operated calcium (Ca2+) entry (SOCE), State of inertia, 461 90, 92, 126–127, 130, 200, 254, Stauderman,K.A.,439 342, 374, 414–415, 422–426, 1-Stearoyl-2-arachidonoyl-sn-glycerol (SAG), 436–445, 584, 586, 679f, 695, 128 739, 850, 890, 910, 914–915 Steinert,P.M.,849 Store-operated channels (SOC), 126, 376, STIM, see Stromal interaction protein (STIM) 393, 414–415, 418, 424–425, Stim and Orai proteins, 417–420 436–438, 441–443, 669, Ca2+ homeostasis, 417 674–675, 678, 688, 692–693, CRAC channels, 418 695–698, 708–709, 711t, 714, CRACM1, 418 718, 750, 764, 783, 882–883, ER Ca2+ sensor, 418 886, 889, 895, 931 knockdown of STIM1 by siRNA, 418 StpA (bacterial protein), 464 Orai1 functional domains, 420t Streisinger, G., 342 STIM1 functional domains, 419t Streptozotocin-induced diabetes mellitus, 259 STIM1 and STIM2, 417 Stretch activated channels (SAC), 71, 158, Stim1-Orai1-TRPC 670f, 688, 691, 694, 709, 718, communication, 421–422 750, 772, 799 aspartates in TRPC1 ((639)DD(640)), Stretch and osmotic swelling, 179, 823 422 Stringent disulphide reduction, 29 CAD (CRAC-activating domain), 421 Stromal interaction protein, 92–93 CCb9, 421 STIM1, 92 CMD/CDI, 421 STIM2, 93 Index 1075

Stromal interaction protein (STIM), 393–394, Structural studies, Budding Yeast, 25–35 417–420, 425–426, 439, 673, Sturgess, N. C., 814 783, 894 S. typhimurium, 463 Structural biology Substance P, 492, 582, 624, 627, 641, 790, 856, with ARD 863–874, 991, 999 TRPA1, 14 Suguro, M., 939 TRPN1, 14 Sukumaran, P., 125–131 TRPV4, 14 Sulphonylurea receptor (SUR), 157–158, 164 coiled coil bundle SUMOylation, 162, 790 antiparallel α helices, 14 Sunesen, M., 107–120 coiled coil stability, 15 Supercinnamaldehyde, 110–111, 111f helix–helix orientation, 15 Superoxide dismutases, 532, 769 heptad residues, characteristic features, SUR, see Sulphonylurea receptor (SUR) 14–15 Surface biotinylation assay, 550, 552, 561 homomeric vs. heteromeric protein Sus scrofa, 222 complex, assembly, 14 Sutton, K. A., 301 hydrophobic interaction, 15 S3 voltage-sensing domain, 214 oligomeric state, 15 Swedish Human Proteome Resource (HPR) parallel α helices, 14 program, 821 partner selection, 15 Swimming pattern, 457 TRPM7, C-terminal coiled coil domain, Syncytiotrophoblast (STB), 251–252, 255t, crystal structure comparison, 16f 910, 913–914, 914f, 918, 922 twofold symmetry, 16 Synthetic antidepressants, 991 EM structures, 7–10, 8f Synthetic modulator fragments, high-resolution structures, 4t broad-spectrum non-natural, synthetic methods and considerations, 4–7 blocker, 90–95 detergents, choice, 6 ACA, 94–95 expression system, cells, 6 2-APB, 92–93 clotrimazole, 95 full length proteins or smaller mammalian and ﬂy receptor-activated fragments, working, 7 TRPC channel, regulation, 91f membrane protein structures at different SKF-96365, 90–92 resolutions, 5f SKF-96365 blocking, concentration- NMR and X-Ray crystal structures, 10–19 response relationship, 92f gating spring of mechanoreceptors, 14 chemical structures, 89f TRPM7 α−kinase domain, 10–12 lanthanum and gadolinium ions as TRPM7 coiled coil domain, 14–16 modulators, 98–100 TRPP2 coiled coil domain, 16–17 selective, 95–98 TRPP2 C-terminal E-F hand, 17–19 clotrimazole effects on TRPC6, TRPV ankyrin repeat, 12–14 TRPM2, TRPM3, and TRPV4 TRPV ankyrin repeat domain (ARD), channels, 95f 13f compounds modulating TRPC perspectives, 19 channels, 96–97 subfamilies, 1–2 compounds modulating TRPM cytoplasmic N and C termini, 3t channels, 97 TRPA, 1 compounds modulating TRPV TRPC, 1 channels, 97–98 TRPM, 1 Syzygium aromaticum (vanilloid eugenol), 45, TRPML, 2 59–60 TRPN, 2 Szallasi, A., 491–509 TRPP, 2 TRPV, 1 T TRP channel subfamilies and transmem- Tachykinin substance P, 999 brane topology, 2f Tachykinin (TK), 640, 999 1076 Index

Tachyphylaxis, 12, 50, 52, 187, 495, 497–500 9-Tetrahydrocannabinol (THC), 56, 69, 190, Takahashi, N., 373–383 192t, 346, 625, 931, 972 Taste buds, 831–832 Tetrameric subunit stoichiometry, 7 detection of chemicals in oral cavity, 832 Tetramers, 9, 15, 17, 30, 150, 174, 174f, like neurons and epithelial cells, 832 244–245, 288, 350, 392, 464, in mammals 470, 476, 519–520, 536, 557, papillae (circumval- 783, 930 late/foliate/fungiform), Tetraspanins, 443 832 T-format instrumentation, 34 PLCβ2 signaling pathway, 832–833 light intensities, 34 50–150 taste receptors cells, 831 kinetics parameter, 34 taste stimuli, detection of thermodynamic parameter, 34 ionic and chemically complex taste TG, see Trigeminal ganglia (TG) neuron stimuli, 833f T98G, 956 salty/sour/bitter/sweet/umami, 832 Thapsia garganica (thapsigargin), 49t, 55, TRPM5, 833 112–113, 126, 130, 393, 403, tTRPV1, 834 421, 425, 441, 552, 601, 673, voltage-gated calcium channels (VGCCs), 678, 679f, 693, 699, 715, 739, 832 783, 851, 889–890, 912–913, Taste system, TRPs in, 831–842 931, 978 PKD1L3/PKD2L1 TRPP channels, THC, see 9-Tetrahydrocannabinol (THC) 836–838 Therapeutic intervention, implications of, TRP-melastatin 5 (TRPM5), 834–836 491–509 vanilloid receptor 1 (TRPV1), 838–842 See also TRP channels, complex regulation Taurodeoxycholic acid (TDCA), 673 of TRPV1; Thermo TRP Taylor-Clark, T., 969–978 channels TCCSUP (urothelial cell line), 956 Thermal activation, energetics of, 472–477 T-cell, 157, 160–161, 787f, 790, 887, 959 Boltzmann distribution law, 473 TDCA, see TAURODEOXYCHOLIC acid closed-to-open voltage-dependent channel (TDCA) transition, 472–473 Temperature-activated TRP channels Gibbs free energy, 472 (ThermoTRPs), 517 energy barrier profile, 472f Temperature -sensitive TRP channels, see open-closed transition, 473 Thermo TRP channels parameters, thermodynamic, 474 Tert-butylhydroperoxide (t-BHP), 586, 769 temperature coefficient, 473 6-Tert-butyl-m-cresol, 627 thermodynamic system, 472 Testicular function Thermal and voltage sensitivity of thermoTRP PKD, 891–892 enthalpic and entropic changes, 475 spermatozoa, 881–882, 885, 888–889, heat-induced single-channel activity of 892–893 TRPV1, 476 TRPC1, 883–884 Ohm’s Law, 476 SOCE channel assembly, 890, 895 patch clamp recordings, 476 TRPC2 and, 885–886 single channel current (bursts), 476 TRPC3 and, 886–888 TM4 of thermoTRP’s, 476 TRPC4 and, 888–889 V0.5, definition, 476 TRPC6 and, 889–890 Q10 for channel gating, 475 TRPM family, 893–894 structural determinants of thermal TRPM4, 893 sensitivity TRPM7, 893 TRPM8, 479–480 TRPM8, 894 TRPV1, 478–479 TRPV family, 892–893 structural determinants of voltage- TRPV 1-6, 893 dependence, 479–480 Tetraethylammonium, 733 thermosensation, 474 Index 1077

threshold, 475 mammalian thermoTRPs, 517 TRPM8 (cold sensor), 475 subfamilies grouped by homology, 517 TRPV1 (thermoreceptor), 475 in normal conditions, 494 TRPV/TRPM/TRPA families, 474–475 temperature activation Thermal hyperalgesia, 66, 492, 494, 503–504, entry of Na+ and Ca2+, 521–522 616–619, 627–628, 648t–650t, heat and cold denaturation, 524 990, 999 polymodal regulation, 523 Thermal hypersensitivity, 373, 617, 637 pore turret, 525f Thermal nociceptive signaling, 197 protein denaturation, 524 Thermal sensitivity, structural determinants of Q10 values, 521 TRPM8, 478 thermodynamic parameters, 522 DRG sensory neurons, in mouse, 478 van’t Hoff equation, 523 membrane lipids, 479 voltage vs normalized conductance methyl-beta-cyclodextrin (MCD), 479 relationships, 522f TRPV1, 477–479 thermal and voltage sensitivity activation by capsaicin and voltage, 478 +2 heat-induced single-channel activity of Ca concentration, 477 TRPV1, 476 cold receptor (TRPM8), 477 structural determinants of thermal FRET, 478 sensitivity, 477–479 hot receptor (TRPV1), 477 structural determinants of voltage- lacking C-terminal, 477 dependence, 479–480 temperature activation, 478 trafficking proteins, 507–509 temperature activation of, 478f TRPV1 trafficking, 503 Thermal sensors, 155, 463 TRPV1 and TRPM8 channel activation by Thermodynamic formalism, 461 agonists, 480–481 Thermo-induced conformational change, 462 TRPV1 channels, 483–485 Thermoregulation, 44, 59, 201, 454, 998 thermoTRP channels undergo pore Thermosensation, 43, 62, 66, 108, 119, 196, dilation, 485 287, 457, 461–462, 474, 539, voltage dependence 616–617, 620f, 627, 691 Arginine residues at S4 segment, 519 Thermosensing, 454, 463, 822 ThermoTRP channels changes on open probability, 523 activation gate, 485–486 gating current recordings, 519 allosteric gating in thermoTRP, 481–483 Hodgkin and Huxley prediction in 1952, 519 allosteric models and activation + allosteric coupling, 525 Shaker K channels, 519 allosteric gating scheme, 525 S4–S5 linker (K856), 520 Cole-Moore effect, 528 S1–S4 voltage-sensor-module, 520 PO values, 528 TRPM8 channels, S4 domain, 520 strict coupling vs allosteric coupling, TRPM8 S4 helix, topology, 521f 527f two-state model, 520 biophysics of polymodal receptors, voltage-gated ion channels, features, 469–486 518 channel gating process weak, 520 Boltzmann equation, 518 voltage sensing, 517–528 conformational change, 518 See also Thermo TRP channels; specific Kv channels, 519 TRPs opened and closed state, 518–519 Thiazide-induced hypocalciuria, 259 Coda, 486 Thick ascending limb of Henle’s loop (TAL), energetics of thermal activation, 472–473 278 family Thin limb of Henle’s loop (TL), 278 allosteric nature, example, 517 Thr-95, 186 features, 518 Thr704, 644 1078 Index

Three-dimensional (3D) structure, 1, 5, 7, 261, intracellular Ca2+ concentration ([Ca2+]i) 420, 639 is, 279 Threonine, 10, 177, 230f, 232, 246, 418, 538, Transitional cell carcinoma (TCC), 935, 950 693, 786, 788, 893 6 Transmembrane helices (TM1-6), 26, 889 Threshold phenomenon, 187 Transmembrane-spanning segment (TM), Throat irritation, 970 50, 150–152, 150f, 154, 316, Thymol, 57t, 59, 330, 627, 853 318–319, 481, 639, 710, 1015t, Thymus vulgaris (thymol), 57t, 59, 330, 627, 1019t, 1022t, 1024t, 1027t 857 Transmural pressure, 694, 717, 772 TIRF, see Total Internal Reflection Tranter, P., 120 Fluorescence (TIRF) analysis Trematodes and cestodes TIRF microscopy, 440 S. mansoni/S. japomonicum/S. haemato- Tissue-culture model in zebrafish, in vivo, bium, 365 349–350 tapeworm (cestode) Echinococcus ER-associated protein degradation multilocularis, 365 pathway, 350 TRP channel genes of Echinicoccus OS-9 expression, 350 multilocularis, 365t Tissue damage, 532, 615, 623–624, 628, 972 TRP channel genes of Schistosoma TKR, see Tyrosine kinase receptor (TKR) mansoni, 365t TK, see Tachykinin (TK) TRPM6 and TRPM7 channels, 366 TlpA protein, 463 Trial-and-error strategy, 6 T lymphocytes, 159f, 160, 178, 414, 437–438, Trigeminal ganglia (TG) neuron, 50–51, 70, 442 186 TM, see Transmembrane-spanning segment Tripterygium wilfordii (Chinese medicinal (TM) herb), 72t, 73 TM1-6, see 6 Transmembrane helices (TM1-6) Triptolide, 72t, 73 TM3-TM4 linker, 156 TRPA, see Ankyrine-rich TRP (TRPA) TM5-TM6 linker, 54, 156 TRPA (ankyrin transmembrane protein), 694, TNFα, see Tumor necrosis factor-α (TNFα) 947 Togashi, K., 93, 818 functions of TRP channels in C. elegans, Topoisomerase I, 456 325–327 Topoisomerase II, 456 in multiple tissues, 326 Törnquist, K., 125–131 TRPA-1/TRPA-2 channels, 326 Total Internal Reflection Fluorescence (TIRF) regulation of TRP channels in C. elegans, analysis, 138 330 TPC, see Two-pore channel (TPC) mammalian TRPA1, 331 “Traffic” model, 212–213, 212f subfamily, 325 Transcellular Ca2+ transport pathway, 242 TRPA1, 520, 972–973, 974–975 Transcriptional mechanism, 463 activation ingredients Transforming growth factor, 768 garlic, 110 mustard oil, 110 Transient inward current (Iti), 162, 790 Transient receptor potential channel C2 wasabi, 110 (TRPC2), 3t, 91f, 99, 125–131, activators, 974 325, 341, 344–345, 374, 392, agonist application, 110 416–417, 423, 505, 549, 578, antagonists, identification, 110 671t, 689, 699, 710, 732, 733t, blockers, 974 735t, 751, 782, 783, 813t, 882, calcium influx requirement, 564 885–886, 890, 910, 911t, 912, in cold pain and hyperalgesia 931, 988 increased expression, 624 Transient receptor potential vanilloid 5 increased intracellular Ca2+, 624 (TRPV5), 278 epidermal permeability barrier homeosta- in DCT2 and CNT, regulation, 279 sis, 855 Index 1079

induces heterologous desensitization of OAG activated TRPC6 channels, 913 TRPV1 PHM1 induction, 912 activated by cannabinoids, 625 TRPC mRNA and protein expression, heterologous desensitization, 626 911t knockout mice, 975 TRPC1/C3/C4/C6/C7 mRNA, in mechanical hyperalgesia expression of, 911, 912 CFA-induced mechanical hyperalgesia, functions of TRP channels in C. elegans, 625 325 Ex vivo skin-nerve recordings, 625 mammalian, 325 mechanical hypersensitivity of colon, trp-1 and trp-2 null worms, 325 625 TRP-1/TRP-2/TRP-3, 325 mediates visceral pain, 625 heteromers, 996 mediates noxious chemicals in zebraﬁsh, homo-/hetero-multimerization, 689 346–347 ion channels, 413–426 cannabinoids, 346 Stim and Orai proteins, 417–420 TILLING, 346 Stim1-Orai1-TRPC communication, trpa1a and trpa1b, 346 421–422 TRPV1 orthologues in chickens and Stim1-Orai1-TRPC complexes, worms, 347 422–426 tissue damages TRP proteins, TRPCs, 416–417 activation, 620f IP3 production, 550 bradykinin, 624 PIP kinase stimulation, 551 formalin, 623 protein kinase C activated, 554 PLC/PKA activation, 624 regulation of TRP channels in C. elegans, pungent cysteine-reactive chemicals, 330 623 CIRB motif, 330 treatment with mustard oil, 563 Gq-PLCβ pathway, 330 voltage-clamp techniques, 564 RT-PCR/Western TRPC, see Classic or canonical TRP (TRPC) Blot/immunoﬂuorescence, TRPC (canonical) channels, 688, 689, 948 690 and cancer, 933–937 stimulus-dependent exocytosis, 553 in Ca(2+) homeostasis and differentia- αII-spectrin, 551 tion, 932 subfamilies (TRPC1-7), 689 DAG-sensitive TRPC1 channels, 931 TRPC1, 549 GAL1 overexpression, 934 TRPC2 (pseudogene in humans), 549 human gastric cancer, 932 TRPC3/6/7, 549, 550 LNCaP cells differentiation, 933 TRPC4 translocation ovarian cancer, 932 EGF pathway, 551 SH-SY5Y neuroblastoma cells, human, TRPC5 translocation 931–932 EGF effect in HEK-293, 550 TRPC1 expression in rat liver hepatoma TRPC6 translocation cell line, 931 α1A-adrenoceptor stimulation, 553 TRPC2 expression in murine B16 EETs application, 552 melanoma cell line, 931 ER-store depletion, stimulation, 552 TRPC6 prostate cancer cell lines, 933 G-protein cascade, stimulation, 552 TRPC6 channels and NFAT, coupled Tyr-959 and Tyr-972, phosphorylation, 551 activation, 931 VAMP-mediated exocytosis role, 552–553 in C. elegans and Drosophila, 554 TRPC1 and TRPC4, 823–824 DHPG stimulation, 552 in frog oocytes, 341 EGF receptor, 550 Human Proteome Research program, 823 endocytosis, 553 intracellular Ca2+ elevation, 577 family involvement in mechanotransduction, 577 GPCR stimulants, 913 mechanosensitive cation channel, 343 1080 Index

TRPC1 and TRPC4 (cont.) electrophysiological properties, 127–129 mGluR1 receptor activation, 576 VNO neurons, 127 NSC’s proliferation, 577 erythroblasts, 127 pore region, mutations, 438 as erythropoietin-evoked signalling vs. STIM1, functional interaction, 112–113 mediator, 130 store-depletion stimulation, 112 knockdown cell, 131 TRPC4, 823–824 males against female, mating, see Mouse TRPC1 mRNA, 823 in mice, 127 Western blot, 822 olfaction, pheromone signal transduction, Xenopus oocyte, 343 129 TRPC1andOrai1toCa2+ entry, contribution as pseudogene in human, 125–126 proposed molecular components in rat thyroid cells, 130–131 Orai channels, 438–439 calcium signalling, 130f STIM proteins, 438 novel calcium entry mechanism, 130 TRPC channels, 437–438 regulation, 126–127 SOCE characteristics Ca2+-entry, 126 activation and assessment, experimental calcium-mediated signalling, 126 methods, 436–437 inward current, reduction, 126 currents associated, 437 Na+-entry, 126 STIM1/Orai1 and CRAC channels ROCE vs. SOCE, 126 TRPC-generated SOC channels sensory activation of VNO, 578 [Ca2+] measurements in cells, 442 as SOC channel, 126 co-immunoprecipitation and TIRF splice variants, see Mouse experiments, 443 whole-cell condition, 128 C-terminal residues of STIM1, 443 TRPC3, 7, 9 experimental observations, 442 atrophy and progressive paralysis exhibited, major conundrum, 442 580 mechanisms, 443–444 BDNF-induced growth cone plasticity, scepticism, 442 involvement in, 579 STIM1 knockdown, 443 dendritic spine formation, 579 STIM1+TRPC1 overexpression, 443 dimension, 9 TRPC1 activation, 443 disparity, 9 TRPC1 knockdown, 443 feed back loop established, 579 TRPC1-SOCE activation, 443 knock-out mice, 989 whole cell patch clamp, 443 modulation mechanism, 9 TRPC1/Orai1/STIM1 and SOC channels multi-modal activation, 9 C-terminus of TRPC1 (639DD640), NFAT activated, 579 440 overexpression, 579 D76A mutant, 441 structure, components, 9 STIM1 knockdown, 441 dense globular inner core, 9 STIM1 polybasic tail (684KK685), 441 sparse outer shell, 9 TRPC2 TRPC3–/–, 795 acrosome reaction activation, 578 TRPC4, 898 action potential recordings, decreased, 578 Ca2+ and Na+ in β-cells, 824 activation hydrolysis of PIP2, 824 receptor-dependent mechanism, 130 5-hydroxytryptamine, activated, 580 store-dependent mechanism, 130 in INS-1 cells and rat β-cells, 823 arachidonic acid generated, 578 involvement in axonal regeneration, 580 as calcium entry regulator in sperm, neurite outgrowth, increased, 580 129–130 role in acute and delayed neuronal injury, CaM binding sites 580 ankyrin, 127 sites enkurin, 127 adrenal glands, 580 Index 1081

endothelium, 580 depolarisation, 287 kidney, 580 monomeric TRP channel subunits, 288 retina, 580 polycystin-1-TRPP2 receptor-channel testis, 580 complex, 288f store-operated Ca2+ entry (SOCE), 824 studies on architecture of, 288 TRPC4α and TRPC4β, 823–824 subfamilies TRPC5 ankyrin transmembrane protein 1 activated by lipids, 581 (TRPA1), 931 CaMK action, 581 canonical/classical TRP proteins knock-out mice, 989 (TRPC), 930 –/– mice, 794 melastatin related TRP proteins neuronal polarity establishment, stages (TRPM), 930 dendritic arborization, 581 mucolipins (TRPML), 930 development into neurites, 581 polycystins (TRPP), 931 extension of neurites to form axon, 581 vanilloid receptor related TRP proteins lamellipodia formation, 581 (TRPV), 930 spine/synapse formation, 581 of thermo TRPs, 491–492 overexpression, 582 TRP domain, 930 TRPC6, 989, 1012–1013 TRP channel family association with multiprotein complex subfamilies Calcinurin (CaN), 582 ankyrin repeat (A), 517 Calmodulin (CaM), 582 canonical (C), 517 immunophilin FKBP12, 582 melastatin related (M), 517 M1AChR, 582 mucolipin (ML), 517 PKC, 582 polycystin (P), 517 Ca2+ entry initiated, 582 vanilloid binding (V), 517 on chromosome 11q21-q22, 1012 TRPγ, 554 dendritic spine formation, effects, 583 TRPM (melastatin), 688, 690–691, 947 expressed in atypical proteinkinase domain/TRPM2/6/7 brain, 582 channels, 919 cardiac neurons, 582 cladogram, different animals, 224f neurons of olfactory epithelium, 582 conventional RT-PCR, 690 retinal ganglion cells, 582 EGF treatment, 563 FSGS, see Focal segmental glomeruloscle- functions of TRP channels in C. elegans, rosis (FSGS) 325 knock-out mice, 975, 989 C. elegans defecation cycle, 324 neurokinin receptors, activation, 582 GON-2, 325 NFAT transcription factors, 1013 GTL-1/GTL-2/CED-11, 326 potential involvement, 583 heterotetramers, 151 P112Q/R895C/E897K, mutations in, 1013 ionic channel TRPM1, 150 vanilloid TRPs, 1014 NSCCa, physiological functions TRPC7 calcium-dependent voltage regulator in bipolar disorder patients, 584 TRPM4, 150 expressed in cold sensor TRPM8, 150 cerebellar purkinje cells, 584 Mg2+ regulated and permeable cerebral cortex, 584 channels, TRPM6 and TRPM7, hippocampal neurons, 584 150 mitral layer of olfactory bulb, 584 redox-sensor TRPM2, 150 pons, 584 taste sensor TRPM5, 150 in mouse brain, 584 permeability regulated by, 563 TRP channels, 287, 930–931 regulation of TRP channels in C. elegans, complex regulation of TRPV1, 491–492, 330 496f GEM-1 and GEM-4, 331 1082 Index

TRPM (melastatin) (cont.) leak current, 113–114 Glu residues, 331 melanin synthesis, 113 GON-2 and GTL-1, 331 NAD, 113 subfamilies (TRPM1-8), 690 necrotic changes, 538 TRPM1, 1017 nucleotide, 113 abnormal bipolar cell activity, 141 overexpression, 538 access to antibodies, 138 oxidant injury to striatal cells, 537 in brain, 141 oxidative stress-induced cell death, 113 C allele frequency rate, 136 oxidative stress modulated, 112, 536 CSNB correlation, 140 and PARP, inhibition, 538 in eye, 140–141 physiological splice variants, 536 function, 140–143 prism-shaped minor component, 9 in situ hybridization, 138 proposed signaling mechanisms, 535f intracellular localization, 138–139 pyrimidine, 113 ion channel, molecular architecture, TRPM3, activation 142 glucose homeostasis, 113 melanocytes and bipolar cells, hepatocytes, activation, 113 necessity, 142–143 pregnenolone sulphate (PS), 114, 820, melanin production, 140 821f melanoma metastasis, 139 sphingolipids, 820 melastatin (MLSN) gene, identiﬁca- sphingosine, 113 tion/characterization, 136 Zn2+ ions, 821 MITF mutations, 137 TRPM mRNA and protein expression, 919t –/– mouse model, 140, 142 TRPM4 and myogenic tone, 717–718 and pigmentation, 140 antisense technology, 718 qRT-PCR analysis, 138 Ca2+ on TRPM4 activity, 718 regulation by mGluR6, 142–143 “myogenic” channels in skin, 139–140 (TRPM4/TRPC6), 718 splice variants, 136–137 “myogenic response,” 717–718 tissue and cellular distribution, 137–139 role of TRPC6, 718 92+TRPM1, 137 stretch-induced VSMC depolarisation, 109+TRPM1, 137 717 TRPM2, activation features TRPM4/5 channels, 718 ADP-ribose, production, 112, 534 and TRPM5 ADPR interaction with TRPM2, 535 amino acid sequence, 814 amino acids 1292-1325 deletion, ATP selectivity, 155 TRPM2-X, 536 ABC transporters, 814 amino acids 538-557 deletion, automated patch clamp, 112 TRPM2-N, 536 Bayliss effect in cerebral arteries, amyloid â-peptide, activation, 537 TRPM4 promotion, 160 bullet-shaped major component, 9 biophysical and regulatory properties, CD38, 538 151–156, 152f–153f current activation, 113f calcium selectivity, 154 in diabetes, 538 [Ca2+]i concentration, 814 endogenous TRPM2 function, chemoreceptive cells, 836 inhibition, 536–537 CICR, 815 exposure to oxidative stress, 536 CRI-Gl rat insulinoma cells, 814 extracellular signals, 534 diacylglycerol (DAG), 834 2+ increase in [Ca ]i, 535 heterologous expression, 151 inhibition results, 538 expression in humans, 148–149 insulin secretion, 113 ﬁring rate of breath pacemaker neurons, isoforms, schematic representation, modulation, 161 537f in humans and mouse, 815 Index 1083

inositol trisphosphate (IP3), 834 cell swelling, 539 insulin secretion, TRPM4 enhancement, ChaK1, 173 158–160, 816 classical kinases, 10 ionic selectivity, 153 coiled-coil region, 27 ionomycin, 114, 114f controversial function, 11 linear current voltage (I/V) relationship, crystal structure, 11f 814 C-terminal cytoplasmic coiled-coil fast/slow oscillations in [Ca2+]i, assembly domain, 27 815–816 C-terminal lobe, 10 by glucose, 816 current densities, 178 GPCRs D1765, 10 main properties, 149t D1775, 10 molecular structure, 149–151, 150f death, 539 NBD, 814 detachment, 539 PIP2, 834–835 expression, observation, 174 PLC signaling pathway, 834 functional characterization, 179–180 rise in [Ca2+]i, 158 growth arrest, 539 T1Rs, sweet and umami stimuli, 834 helix content, estimate, 173 T2Rs, bitter stimuli, 834 inhibited by Mg2+ and Zn2+, 538 temperature sensitivity, 835, 835f K1646, 10 thermal, PIP2 and pH selectivity, α-kinase, 27 154–156 α-kinase domain, 10–11 TRPM subfamily, 834 LTRPC7, 173 voltage selectivity, 154–155 NOD, 174 PI-PLC, 814 targeted deletion vs. global deletion, PKC and PIP2, 815 178 putative calmodulin binding sites, 151 TRP-PLIK, 173 putative phosphorylation sites, 151 Mg2+ deﬁciency, 539 in stimulus-secretion coupling in monomer components, 10 β-cells, 815–816 nonmuscle myosins, involvement, 177 TRPM4 in cardiac cells, 162–165 N-terminal lobe, 10 TRPM4 in immune cells, 160–161 overexpression TRPM5 as taste transducer, 163–164 pathological functions in disease TRPM5 knock-out mouse, 815 conditions, 179–180 TRPM5 mRNA, 815 pharmacology, 156–157 TRPM5 activation, 156 phosphorylation, 177 unusual features, 112 physiological impact, 158–164, 159f TRPM6, 175, 177t PIP2 hydrolysis, 177 TRPM7, activated by low levels of PLC members, interaction, see MgADP, 538 Phospholipase C (PLC) activity alternatives, 173 p38 MAPK and JNK, 178 architecture and expression pattern, potential mechanosensor, 179 173–175 Q1767, 10 autophosphorylation, 177 role in anoxic injury, 539 BALB/c animal, 174 spontaneous, magnesium-subtracted cardiac expression, 174 current, 176f cations, permeability, 175 suppression in primary cortical neurons, C57/Bl mice, 174 539 channel properties and regulation, tetrameric architecture, 15 175–178 TRPM6/TRPM7, formation, 176 cell survival, 178 TRPM8 activation, 534, 691, 973–974, cellular and biological functions, 974, 976 178–179 agonists, 191t–192t 1084 Index

TRPM (melastatin) (cont.) Wilms’/rhaboid tumours and antagonists, 191t–194t rhabdomyosarcomas, 939 automated patch clamping, 115 TRPM4 expression in CD5+ lymphomas, biophysical/pharmacological properties 939 and modulation, 187–195 trpm1 gene, tumour suppressor, 937 activation features, 187 TRPM1 (melastatin), 937 + α2A-adrenoreceptors, 188 TRPM7, Mg2 -sensitive, 939 agonists, identiﬁcation, 188 expressed in breast tumors, 939 Ca2+-dependent desensitization, 187 trpm8 oncogene, 938 for chronic pain, 197–203 TRPM channels in vasculature, 707–723 cold detection, 196 activation mechanisms/functional roles cold hypersensitivity, 197–198 TRPM1, 712 cold sensation compounds, 115 TRPM2, 712–713 cold temperatures, 114 TRPM3, 713 ER membrane, expression, 200 TRPM8, 714 eucalyptol, 114 TRPM4 and TRPM5, 713 functions, 188 TRPM6 and TRPM7, 714 gene, structure/function and expression, biophysical properties, 710–712 186–187 ion selectivity, 712 icilin, 114 linear current-voltage (I-V) relation, -independent mechanism, 198 712 membrane depolarisation, 712 KO mice, role in cold sensing, 196 patch-clamp measurements of cation lipid rafts, 188 currents, 710 menthol, 114 channel structure, 710 menthol block, characterization, HEK293 or CHO cells, 710 116f–117f homotetramerisation, 710 menthol/cooling compound, effects, long TRPs, 710 197–198 N-terminus and C-terminus, 710 modulation factors, 188 transmembrane (TM) domains, 710 as molecular sensor of cold TRPC/TRPV/TRPA/TRPN channels, temperatures, 195–196 710 –overexpressing cancer cell, 201 TRPM6/7 heterotetramers, 710 polyphosphates, 188 TRPM roles in native cells protons, 188 (VSMC/ECs), 710 physiology/pathophysiology/therapeutic vascular melastatin TRPM channels, target potential, 194–201 expression/properties of, 711t for prostate cancer, 199–200 GPCR/Ca2+ store depletion, roles of, QPatch systems, 115 714–715 sensory neurons, expression, 197 pharmacological properties, 715–716 TG and DRG neurons, expression, 198 inhibitor of TRP channels, 715 voltage ramp protocols, 115 TRPM3, 715–716 zinc-binding module, 11 TRPM8, 716 TRPM channels and cancer, 937–938 TRPM6/7 channels, 716 HEK293 cells, 937 vascular function/disease, 716–723 heterologous expression, 937 TRPM2 (LTRPC2) microphthalmia transcription factor and β-cells, 817 (MIRF), 937 anti-TRPM2-N and anti TRPM2-C, 817 TRPM8 expression, 937–938 cytoplasmic ADP ribose (ADPR), 817 cold sensor in prostate, 938 long form of channel (TRPM2-L), 817 immunohistochemical experiment, 938 short form of channel (TRPM2-S), 817 single-cell RT-PCR experiment, 938 Western blot, 817 TRPM5 expression in and β-cells death, 820 Index 1085

alloxan-induced oxidative stress, 820 vasoconstrictor/vasodilator influences, 721f short isoform of TRPM2 (TRPM2-S), TRPML, see Mucolipidin group (TRPML) 820 TRPML (mucolipin), 323, 688, 948 heat, 819 functions of TRP channels in C. elegans, intracellular Ca2+ release channel, 820 325 in stimulus-secretion coupling in β-cells, CUP-5, 325 817–819 TRPML1, 325 activation of TRPM2 channel, 818 PPK-3 (phosphatidylinositol phosphate ADPR/Ca2+/NAADP/NAAD, effects kinase 3), 330 of, 818 regulation of TRP channels in C. elegans, Ca2+-activated channel, 818 330 cADPR, high concentrations of, 818 CUP-5 activity, 330 insulinotropic agents, 819 TRPML1, 222, 1026–1027 modulators of TRPM2 activity, 819 active shRNA expression system, 216 N-(p-amylcinnamoyl) anthranilic acid acute knockdown, effects, 216 (ACA), 819 ALG-2 protein, role, 215 reactive oxygen species (ROS), 818 c.1_788del (genomic deletion), 1026 TRPM2 in oxidant stress/endothelial on chromosome 19p13.3-p13.2, 1026 permeability, 717 -deficient murine macrophage, 216 oxidative and nitrosative stress, 717 dendograms of, 223f TRPM2 activation by H2O2, 717 discovery and initial characterization, TRPM2/7 channels, 716 209–213 TRPM2-S (short), 536 endocytic pathway functions, 210–211, 216 TRPM2-TE (tumor-enriched), 536 experimental systems used to report, 211t TRPM7 in embryonic development, functions Fe2+ permeability, 215 of, 351–352 function, specific aspects, 215 endogenous TRPM7 protein in genome sequencing, 223 melanophores, 352 IVS3-2A_G and g.511_6943del mutations, loss-of-function alleles of trpm7, 351 1026 melanin synthesis, 352 key paradigms and questions, 216f mutations in TRPM6 gene, 351 Knockout Mcoln1–/– mice, 1027 scale ENU mutagenesis screen, 351 MLIV, genetic deteminants, 209–210 TRPM7 in magnesium homeosta- mucolipidosis type IV (MLIV), 1026, sis/hypertension, 718–719 1027t in ECs, 719 mucolipin subfamily, 1026 in VSMCs, 719 perspectives, 219–221 TRPM8 in thermal behaviour of blood vessels, PKA-dependent phosphorylation, 212 719–723 pre-lysosomal trafficking defects, analysis, calcium responses, 719 214 effects of TRPM8 agonists, 720 recent developments, 214–215 functional expression in rat tail artery consequences, identification groups, VSMC, 720f 214 menthol structure-function analysis, 214 cutaneous circulation, 722 “traffic” and “metabolic” models, 212–213, dilatory effects of, 722 212f effects in vessels precontraction, 721 endocytic pathway, 213 -induced [Ca2+]i rise, 720–721 TRPML2 patch clamp recordings, 722 biological roles of, 227 STOCs, 722 CD59, recycling, 226–227 protein expression channel formation, 221 Abcam anti-TRPM8 antibodies, 719 channel properties, 225–226 Alamone anti-TRPM8 antibody, 719 early endosome marker TRPM8 receptor mRNA in rat, 719 EEA1, 226 1086 Index

TRPML2 (cont.) schematic diagram, 230f Rab5, 226 in vitro experiments, 234 endocytosis regulation, 221, 226–227 in vivo experiments, 234 endosome marker Western blot analyses, 230 CD59, 226 Trpml4, 222 MHCI, 226 TRPN (NomPC-like), 948 ER marker TRPN1 (NOMPC), 341 ER-YFP, 226 TRPN (NOMP-C homologues), 26 exocytosis regulation, 221, 227 TRPN (TRP-NompC) subfamily, 323 genome sequencing, 223 functions of TRP channels in C. elegans, genomics, 222–224 325 Golgi marker mechanosensation, 327 GFP-Golgin 160, 226 TRP-4, 326 GGA3-VHSGAT-GFP, 226 regulation of TRP channels in C. elegans, late endosome marker 330 CD63, 226 TRPP, see Polycystin group (TRPP) Rab7-HA, 226 TRPP (Polycystin), 287–303, 688, 691, 948 lysosome marker ADPKD, 287–290 Lamp 3, 226 in humans, 892 Lysotracker, 226 family, 292, 919–921 Rab 11, 226 co-immunoprecipitation, 920 in vertebrates, 221 colchizine, 920–921 phylogeny, 222–224 cytochalasin D, 920 plasma mebrane, heterologous expression, ion channels, 292 226–227 mammalian homologues secretory vesicle marker functions of TRP channels in C. elegans, Rab8, 226 325 subcellular localization, 226 PKD-2, 325 subunit interactions, 227 gene encoding (PKD2L2), 299–300 tissue distribution, 224–225 mRNA in mouse testis/oocytes, 300 TRPML3 mRNA and protein expression, 920t characteristics of, 231t comparative genomics, 222 PKD1L1, 301–302 disease causes, 222 PKD1L2, 302 endocytic pathway roles of, 234–235 PKD1-like (TRPP1-like) proteins, 691 endosome acidiﬁcation and differentiation, PKDREJ, 300–301 235f polycystin-1 family, 292–293 endosome marker primary cilia and PKD, 295–296 dextran, 234 regulation of TRP channels in C. elegans, EEA1, 234 331–332 Hrs, 233 mammalian TRPP2 and PKD1, 331 genome sequencing, 223 PKD-2 and LOV-1, 331 genomics, 239–231 TRPP1 and TRPP2, 691 heterologous expression systems, 233 PC1 and PC2, 691 homologs, 230 PKD1 and PKD2, 691 immunohistochemistry, 230 polycystin 1 and polycystin 2, 691 melanocyte marker TRPP2 and PC-1, 293–297 HMB45, 230 TRPP3 and PKD1L3, 297–299 tyrosinase, 230 TRPP2 (PKD2), TRPP3 (PKD2L1) and molecular physiological function of, TRPP5 (PKD2L2), 919 233–234 6-membrane spanner, 919 orthologs, 229–230 ovulation simulation, 921 RT-PCR expressions, 230 Pkd knockout models in mouse, 921 Index 1087

polycytins PKD-1 and 2 in fallopian Xenopus oocytes, 17 tubes and oocytes, 920 TRPP2 C-terminal fragment (G833–G895), 17 reactive oxygen species (ROS), 920 TRPP2 homologs in other yeast, 319 TRPP2 TRPP3 and PKD1L3, 297–299, 892 in ADPKD, 292 HEK293T cells, over-expression of, 302 encoded by PKD2L2, 292 human TRPP3 channel activity, 303 features, 292 krd mouse model, 297–298 PC 2 encoded by PKD2 gene, 292 multi-exon PKD2L1 gene, 297 regulation, 921 murine TRPP3, 299 six transmembrane segments (S1–S6), Pkd2l1 deletion, 297 292 polycystin L or PKDL, 297 TRPP3 regions of homology, 297 polycystin L encoded by PKD2L1, 292 sour taste receptor, 298 TRPP5, 300 Xenopus laevis oocytes, 297 TRPP1=PKD2, 1023–1025 TRP receptor supefamilies ADPKD and mutations, 1024t, 1025 subdivsions of, 493 on chromosome 4q21-q23, 1023 TRP signalling, regulation Knudson’s model, 1025 ion channel trafficking, 549t mucolipin TRPs, 1025 signalling pathways regulating TRPML1, 1025 translocation TRPML subfamily, 1025 TRPA1, 563–564 polycystin-1 and polycystin-2, 1023 TRPC channels, 549–556 TRPP2, 891–892 TRPM channels, 562–563 ADPKD morbidity and mortality, 296–297 TRPP2 and TRPML channels, proteins anterograde transport, 295 regulating, 564–565 chemosensor, 296 TRPV channels, 556–562 in cilium, activation of, 296 TRP channels, translocation, 548t cyst-proteins, 296 TRPP2 and TRPML channels, proteins features of, 293–294 regulating, 564–565 flow-dependent cytosolic Ca2+ response, TRPV, see Vanilloid receptor-related TRP 296 (TRPV) functions, 294 TRPV (vanilloid), 689–690, 948, 989–990, HEK 293 cells, 17 992–994, 996–1000 heteromeric complex, 17 in cancer progression intra-cellular trafficking, 295 expression profiles of, 950 PC-1, 293–296 channels in tumor growth, 948–949 EGF receptor stimulation, 294 TRPV1, 949–954 expression and localisation, 294 TRPV2, 954–956 induced PI3-kinase activity, 294 TRPV3, 956–957 signalling pathways, 295 TRPV4, 957–958 3-stranded complex, 17 TRPV5, 958 subcellular compartments, 294 TRPV6, 959–960 in tisssues, 294 subfamilies (TRPV1-6), 690 topology of, 295 TRPV1 mRNA, 689 and TRPML channels TRPV1 (VR1), 689 casein kinase 2 phosphorylation site, TRPV2 mRNA, 689 mutation, 564 TRPV4 mRNA, 689 lysosomal degradation, 565 TRPV5 and TRPV6, 689 phosphorylation at N-terminal region, TRPV1, 7–9, 12–13, 518, 823, 949–954, 564 970–971, 973, 977–978, PKD-1, 564 989–990, 992–994, 996–1000 STAM-1 or Hrs, overexpression, 565 activation, 957 TRPML1 mutation, 565 Ca2+ influx, as activating enzymes, 494f 1088 Index

TRPV1 (cont.) modality specific TRPV1 antagonists, capsaicin receptor, 492f 654–655 in central terminals of primary afferents structure-guided drug discovery, and CNS 655–656 immunoreactivity, 618 GABAA-receptor associated protein inflammation/nerve constriction injury (GABARAP), in cell membrane, in rats, 619 508f 12-(S)-HPETE, 619 gene and protein structure co-expressions of, 492 from gene to structure, 638–639 cryo-EM approach, 31 identification as ion channel, 657 data appearance in heat pain and thermal hyperalgesia, IonFlux, 115 616–617 IonWorks, 115 ion channel properties Patchliner, 115 activation, 641–642 PatchXpress, 115 function modulation, 643–644 QPatch, 115 gating biophysics, 642–643 decreased arthritis-induced pain, 618 ion selectivity and permeability, 643 in deep tissue pain membrane topology, 638f arthritis-induced pain decreased, 618 molecular mechanisms, 493–494 “defunctionalisation” of, 493 capsaicin injection, 618 monodisperse homotetramer, 30 carrageenan injection, 618 mRNA, 952, 954 chemokines (CCL2), 618 mRNA expression, 951 cytokines (TNFalpha), 618 and nociception mechanical hyperalgesia, transduction capsicum example, 492–493 of, 618 dorsal root ganglia (DRG), 491 mouse colon afferent fibers, pharmacology and druggability mechanosensitivity, 618 agonists, 646 deficient mice (TRPV1−/−), 950 antagonists, 647, 648t–650t -dependent G0/G1, 950 preferential orientation, 30 -dependent nitric oxide synthase (iNOS), protein-to-lipid ratios, measurement, 30 954 research toolkits -dependent tumor cell apoptosis, 953 clinical status, 647–648 dephosphorylation electrophysiology, 645 PIP2 depletion, 499–500 florescence imaging and 45Ca2+ flux PKA sites, 495–497 assays, 645–646 PKC sites, 497 production and purification, current desensitization of, 493 methods, 644 molecular mechanisms, 501–505 radio ligand binding assays, 644–645 physiological functions, 500–501 resinaferatoxin (agonist), 30 epidermal permeability barrier homeosta- signalling modulation, 505–509 sis, 855 proteins expression, 954 SNARE complex proteins, 506–507 nociceptor, 115 scaffolding proteins, 505–506 pain sensing neuron, 1115 trafficking proteins, 507–509 expression pattern and biological function stable transfection with HEK293 cell, 117f modulation of expression, 640 therapeutic approaches physiological and pathological roles, agonists, 621 640–641 selective antagonists, 621–622 tissue distribution, 639 selective silencing of nociceptors, functional protein, presence, 30 622–623 future prospect therapeutic intervention, 489–491 antibodies and toxins, biologics, 655 TRPV2, 822–823, 948, 954–956, 978 Index 1089

insulin secretion, 823 maternal-fetal Ca2+ transport, 251–252 in mouse insulinoma MIN6 cells and mRNA, 960 β-cells, 822 non-genomic actions of, 246 mRNA, 955–956 pathological and therapeutic conditions siRNA, 955 in cancer, 254–257 TRPV3, 12, 520, 956, 977 in diuretics, 259–260 TRPV4, 7–9, 12–13, 520, 957–958, 978, 1014 glucocorticoids, 258–259 activation in Pseudohypoaldosteronism type II 4α-PDD, 118 (PHAII), 257 endocannabinoids, 117 phylogenic tree of, 241f hypotonicity (cell swelling), 118 physiological condtions, regulations polymodality, 118 aging, 249 stimuli integration, 118 exercise, 249 activator GSK1016790A, 978 lactation, 248 epidermal permeability barrier homeosta- low dietary Ca2+, 248 sis, 855 pregnancy, 248 human disorders, mutation linked, 14 sex hormones, 248–249 See also individual entries SNP data, African population, 260–263 IonWorks, 119 in uterine, 252 mRNA expression, 957 vitamin D regulation PatchXpress, 118 in humans, 246 protein, 957 in mouse, 245–246 systemic osmotic pressure, regulation, 118 TRPV1 and TRPM8 channel activation by TRPV5, 26, 249, 958 agonists, 480–481 in bone resorption, 252–253 mammalian and avian TRPV1 channels, calcitonin regulation, 247 comparison, 480–481 Ca2+ transporting, 239–241 polymodal thermoTRP’s, 481 gene knockout studies, 249–251 single mutation I550T, 481 genes evolution, 240–242 TRP vanilloid subtype 1 (TRPV1), see in inner ear function, 253 Capsaicin (CPS) kidney function and, 242 TRPV6b, 959 Klotho functions, 247–248 TRPV channels pathological and therapeutic conditions functions of TRP channels in C. elegans, in cancer, 254–257 325–326 in diuretics, 259–260 AWA/ASH-mediated sensory glucocorticoids, 258–259 behaviors, 325 in Pseudohypoaldosteronism type II OCR channels, 326 (PHAII), 257 OSM-9, 325 phylogenic tree of, 241f as polymodal sensors, 326 PTH, 246–247 mRNA and protein expression, 916t SNP data, African population, 260–263 NCC involvement, 561 African–Americans vs. European– regulation of TRP channels in C. elegans, Americans, 260–263 330–332 in vertebrates, 241 Asp or Glu, 330 TRPV6, 12, 26, 278–279, 959–960 bisandrographolide (TRPV4), 330 in birds and mammals, 242 camphor (TRPV3 and TRPV1), 330 Ca2+ transporting, 240–241 cannabinol (TRPV2), 330 in exocrine organs, 253–254 capsaicin (TRPV1), 330 gene knockout studies, 249–251 carvacrol, thymol and eugenol genes evolution, 241–243 (TRPV3), 330 in inner ear function, 253 GRK-2 (G protein-coupled receptor intestinal Ca2+ absorption, 278–279 kinase-2), 330 Klotho functions, 247–248 OSM-9 and OCR-2, 330 1090 Index

TRPV channels (cont.) endocytosis, 560 RGS-3 (regulator of G protein phosphorylation, 560 signaling), 331 Rab11 colocalization, 561 sites serine protease tissue, see Kallikrein intestine, 556 SGK1/3 effects, 561 kidney, 556 surface biotinylation, 561 pancreas, 556 TRPV5 trafﬁcking, 560 placenta, 556 TRPV5/6, 690 subfamilies (TRPV1-6), 690 Annexin A2, 918 TRPV1, 689, 914–915 17β-estradiol treatment, 917 activated by capsaicin, endocannabi- calcium selective cation channels, 917 noids and anandamide, Cyclophilin B induced activation, 918 914 double knock-out of trpv6 and ephb6, anandamide binding receptors (CB1, 918 CB2), 915 endogenous expression, 917–918 cervical ripening, 914 functional heterotetramers, 917 cAMP level in cells increased, 497 heterologous expression, 918 enhanced activity, 497 mice lacking TRPV5 are fertile, 918 human pancreatic cancer, 935 osteoclastic bone resorption, TRPV5, human prostate cancer cells, 935 918 pheochromocytoma derived PC12 cell ruthenium red and magnesium line, 935 treatment, 918 premalignant (leukoplasia), 935 TRPV5/6 expression, hormonal control, Src kinase phosphorylation, 557 917 translocation, 557 trpv6 transcription by progesterone, TRPV1-4 (“Thermo-TRPs”), 554 917 TRPV2 translocation Xenopus laevis oocytes, 918 -dependent cell migration, 558 TRPV1 channels, 481–483 RGA overexpression, 559 in HEK293 cells, 483 TRPV2 expression, 936 node of Ranvier, 482 cathepsin B expression, 936 organic cations, 481 MMP9 induction, 936 permeability ratio P TRPV2/3 transcription, 915 NMDG/PNa, 482 TRPV3 pore widening, 482–483 calcium-permeable temperature- thermoTRP channels undergo pore sensitive, 935 dilation, 483 TRPV4, 690 and cancer, 933–937 activated by cytochrome P450, 559 expression in LNCaP cells, 934 binding with PACS-1, 559 homotetrameric structure, 934 cilliary beat frequency autoregulation, human Jurkat T leukemia cell line, 934 917 K562 erythroleukemia cell line, 934 dysfunction results in infertility, 917 prostate cancer clinical outcome expression, 936 prediction, 933 mechanotransduction process, 917 TRPV1-mediated pain and inﬂammatory osmo- and mechanosensitive channel, process, 98 915 in cutaneous sensory system, 853–854 PACSIN3 overexpression, 559 in hair, 853 phospholipase A2 dependant pathway in human epidermis, 848 activation, 917 in peripheral nervous system., 848 WNK1 and WNK4 role, 559 in sebaceous gland, 853 TRPV5, 556, 559 See also Epidermal keratinocytes Ca2+ elevation, 560 TRPV2 gene, 954–955 dynamin-dependent endocytosis, 560 TRPV4 concentration-response curve, 91 Index 1091

TRPV4 knockout (KO) mice, 60, 990, 993, cell proliferation, inhibition, 139 998–1000 differentiation, promotion, 139 bone development, disorders, 60–61 Two-component regulatory system, 455 channelopathies, 61 Two-hybrid screening, 382 in vivo studies Two-pore channel (TPC), 380 central osmosensation, 60 Two-state model, 520, 522, 524 mechanical and osmotic nociception, Type 2 diabetes, 539 contribution, 60 Tyr-295, 186 TRPV4 (OTRPC4/VR-OAC/VRL-2/TRP-12), Tymianski, M. A., 179 821–822 Tyrosine kinase phosphorylation, 186 antibody development by HPR, 822 Tyrosine kinase/PLC/IP3 pathway, 160 human islet amyloid polypeptide (hIAPP), Tyrosine kinase receptor (TKR), 392, 393 822 Tyrosine phosphatase-L1, 380 immunohistochemistry, 822 Tyrosine phosphorylation, 380, 532, 582, 788, osmo and mechanosensors, 822 882, 886, 890 phorbol derivatives, 822 SNPs, 978 U TRPV4/TRPP2, heteromultimer of, 349 Ullrich, N. D., 154 co-immunoprecipitation, 349 U87MG glioma cells, 955–956 deflection of primary cilium, 349 U373MG glioma cells, 952, 956 fluorescence resonance energy transfer Upstream activation mechanisms, 382 (FRET), 349 Urinary bladder mechanisms polycystic kidney disease, 349 degenerin/ENaC family, 869–870 role for TRPV4 in flow sensing, 349 acid-sensing ion channels (ASICs), 870 TRPV5 promoter for generation of transgenic in rabbit bladder epithelium, 870 mouse models, 277–285 mechano sensitive channels, 864f Cre recombinase expressing mice mechanosensory transduction, 863t generation, 283–284 sensory nerve endings, 861–864 perspectives, 285 Smooth muscles, detrusor, 865–866 validation, 284 TRP channels in EGFP expressing mice P2X3 receptor, 871 mouse generation, 279–280 TRPA1, 868 perspectives, 283 TRPM8, 867–868 studies in TRPV5-EGFP mice, 281–283 TRPV1, 866–867 validation, 280–281 TRPV2, 867 TRPV6 gene, 242, 246, 245–246, 260, 263, TRPV4, 868–869 280, 918, 959 two-pore-domain K+ channels (K2P or TRPY sub-family, 26 KCNK), 870–871 TRPY1 (YVC1), 35 urothelium, 864–865 gating control, aromatic residues, 35 Urochordates, 223, 351 Tsavaler’s hypothesis, 938 Urothelial cells, 641, 862–867, 864f, 869–870, Tsavaler, L., 938 937, 954, 957 Tsutsumi, M., 847–856 Uterine contractile activity and TRP, 698–699 TtT/M87 macrophages, 977 myometrial hyperplasia and hypertrophy, Tumor cells, 536, 893, 931, 935–946, 948, 953, 699 955, 959–960 PMH1, 698–699 Tumorigenesis, 929, 939–940, 948 RT-PCR analysis in human myometrium, Tumorigenic cells, 677–678, 933, 948 698 Tumor necrosis factor-α (TNFα), 380, 382, SOC-mediated Ca entry (SOCE), 698 534, 618, 736, 739–741, 764, VOC, role of, 698 820, 976 Western blot analysis and immunolocaliza- Tumor progression, 935, 948, 950t, 952, 954 tion, 698 Tumor suppressor function, 139 Uterine natural killer (uNK) cells, 915 1092 Index

UVB radiation, 140 amiloride-insensitive component, 839 Uversky, V. N., 459 amiloride-sensitive omponent, 839 signaling in peripheral taste receptor cells, V 839 Valente, P., 489–507 Vanillotoxin, 48t, 53 Varitint-waddler (Va and Va J ) mutant Vannier, B., 126 anatomy, 232 Vascular endothelial cells cellular defect, 232 angiogenesis and blood vessel formation physiology, 232 femoral artery ligature, 768 Van Abel, M., 958 HUVECs and HMVECs, rise in, 768 Vandebrouck, C., 751–752 remodeling and patterning, 768 Van der Waals interaction, 16f, 460 siRNA or inhibition of TRPM7, 768 Vanilla planifolia (vanillin), 50, 58t, 60 TRPV4 in collateral artery formation, Vanilloid compounds 768 Arg114, 638f, 642 vasculogenesis, 767 Glu761, 638f, 642 endothelial TRP fields, future development, Ser512, 638f, 642 774 Tyr511, 638f, 642 functional roles, 774t Tyr550, 638f, 642 Ca2+ influx and electrogenesis, Vanilloid receptor, 44, 532, 616, 642, 646, 763–765 650t, 653, 760, 782, 787, mechanosensing 838–841, 866, 892, 914, 950, anti-apoptotic effect, 770 971, 989 ciliary structure, 771 Vanilloid-receptor-like protein 1 (VRL-1), 56, CYP epoxygenase activity, 771 240, 866, 869, 930 exposed to circumferential stretch, 772 Vanilloid receptor-related TRP (TRPV), 1, flow-induced Ca2+ influx, inhibition, 12–15, 26–27, 32, 34, 43, 771 88, 91, 93, 97–99, 115, 117, hemodynamic blood flow, 770 240–241, 242, 278, 289, 321, ion channels, 770 323–325–326, 330, 342, 364t, mechanosensitive signaling pathway(s), 365, 365t–366t, 375, 389, 771 414, 457, 463–464, 469–470, TRP channels, activation, 770–771 471f, 474, 484, 493, 539–540, TRPC1 heteromultimerization, 771 547, 556–562, 575, 603, TRPV4 in pressure sensation, 771 616, 639, 643, 676, 688–690, 694, 709–710, 732, 750, 752, vasodilatory effect, 771 754–755, 760, 762t, 782, 786, oxidative stress 822, 838, 841, 882, 883t, hydrogen peroxide (H2O2), 769 · 892–893, 911f, 914–920, hydroxyl radicals (OH ), 769 914f, 933–937, 947–961, 974, lipids and proteins, redox modifications, 976–978, 988–990 769 Vanilloid receptor subtype 1 (VR1), 127, 240, peroxynitrite (ONOO–), 769 616, 637, 642, 646, 653, 689, superoxide (O2–), 769 838–839, 842, 971, 989 TRP channels/endothelial dysfunc- Vanilloid receptor 1 (TRPV1), 838–841 tion/diseases calcium regulation, 839 angiogenesis-associated diseases, capsaicin, 838–839 progression, 772 cytosolic calcium in taste cells, 839–840, chronic obstructive pulmonary disease, 840f 772 epithelial sodium channel (ENaC), 839 endothelial barrier disruption, 772 FCCP-induced calcium, 840f endothelial dysfunction, 773 knock out mouse, 839 endothelial NO synthase expression, salt taste transduction, 839 reduced, 773 Index 1093

endothelium-dependent relaxation specific functions of TRPM channels, impaired, 772 717–723 excessive oxidative damage, 772 TRPM4 and myogenic tone, 717–718 high pressure ventilation, 772 TRPM7 in magnesium homeosta- hypertension, 772 sis/hypertension, 718–719 lung epithelial-endothelial permeability, TRPM2 in oxidant stress/endothelial 772 permeability, 717 lung injury, 772 TRPM8 in thermal behaviour of blood in mice with inherited hypomagne- vessels, 719–723 semia, 773 TRPM expression in endothelial/VSMC, NO availability decreased, 772 716–717 TRPC3 dysfunction, 772 gene expression, studies of, 716 TRPM7 dysregulation, 773 TRPM8 expression, 717 TRPP1 and TRPP2, malfunction, TRPM mRNA expression (RT-PCR 772 analysis), 716 TRPV4 activation, 772 Vascular hyperplasia, 796 vascular permeability increase, 772 Vascular occlusive disease, 796 TRP isoforms, expression of Vascular smooth muscle cell (VSMC), 90, 112, 183, 394, 397, 399–40, 416, bovine aortic endothelial cells, 760 422, 668, 677, 708–712, 711t, human pulmonary artery endothelial 714–721, 720f–721f, 764–765, cells, 760 782, 784f, 793, 796–799, 890 reported heteromeric TRP channels, Vascular system and TRP, 691 763 in vascular contractile function, 692–698 vascular permeability, control of pulmonary artery hyperreactivity, cytoskeletal stress fiber formation, 696–696 767 SMC proliferation, 397 endothelial barrier function aberration, TRP and HPV, 695 766 TRP and myogenic tone, 694 endothelial hyperpermeability, 767 TRP and pulmonary hypertension, 697 in lung capillary endothelial barrier, TRP in smooth muscle contrac- 767 tion/relaxation cycle, 692–696 lung distention, 767 and vascular SMC growth and hyperplasia, lung filtration and edema incidence, 692 767 TRPC1 specific TIE3 antibody, 692 in mouse model of spinal cord injury, TRPC1/TRPC6 expression level and 766–767 SOC activity, 692 paracellular pathway, 766 TRPM6 and 7, 692 post-trauma capillary dysfunction, Vasculogenesis, 767 767 Vasopressin, 159, 278, 548, 551, 638, 669, pro-inflammatory agents, 766 913, 994 transcellular pathway, 766 VDCa-activating depolarization, 160 vascular tone, control of VDNa, see Voltage dependent Na+ channel + [Ca2 ]i elevation, 765 (VDNa) guanylate cyclases stimulation, 765 VDRE, see Vitamin D responsive element knock-out animals, impairment in, (VDRE) 766 VEGF, see Vascular endothelial growth factor SKCa and IKCa activated, 766 (VEGF) TRPA1 stimulation, 766 VEGF antibodies, 796 Vascular endothelial growth factor (VEGF), VEGF-induced cell migration, 796 347, 763–769, 791, 795–795, Venkatachalam, K., 401 887, 891 Ventral tegmental area (VTA), 995–996 Vascular function and disease, 716–723 Verapamil, 738, 978 1094 Index

Vertebrata, 2140 VSMC, see Vascular smooth muscle cell Vertebrate TRP channel superfamily (VSMC) TRPA (TRP-Ankyrin), 322 VSM cells, 798 TRPC (TRP-Canonical), 322 TRPML (TRP-MucoLipin), 322 W TRPM (TRP-Melastatin), 322 Waardenburg syndrome, 137 TRPN (TRP-NompC), 322 Wagner, T. F., 97 TRPP (TRP-Polycystin), 323 Walker B form of domain, 151 TRPV (TRP-Vanilloid), 322 Walter, K. A., 245 Vetter, I., 41–73, 576 Wang, G. H., 343 + VGCC, see Voltage-gated Ca2 channels Wang, Y.-X., 731–742 (VGCC) Warburgia ugandensis (warburganal), 46t, 52 Vibrissal Merkel cells, 627 Warmth sensation threshold (WS), 188, 189t, Vitamin D receptor (VDR), 918 653 knock out mice, 989 Wasabi, 66, 67t, 110 Vitamin D responsive element (VDRE), 246 Weinberg, R. A, 930 Viitanen, T., 125–131 Welsh, D. G., 718 Vistoli, Dr. G., 486 Wensel,T.G.,25–35 Vlachova, V., 477 Westberg,C.V.,285 Vm, see Membrane voltage (Vm) Western clawed frog (Xenopus tropicalis), VNO, see Vomeronasal organ (VNO) 221–222, 351 + VOCCs, see Voltage-operated Ca2 channel Wet-dog shake, 196–197 (VOCC) White,J.G.,324, 740 Voets, T., 479, 482, 520, 523, 527 Whole-cell patch clamp method, 107–108, 112 Vogel, P., 301 recent technological advances, 108 Voltage-dependence, structural determinants Wicks, N. L., 135–143 of, 479–480 Wigge, P. A., 456 Gouy-Chapman-Stern equation, 480 Wild-type (WT), 16, 98, 126, 129, 138, 175, TM4-TM5 linker, 479, 480f 196–197, 233, 247, 252, 257, Voltage-dependent gaiting mechanism, 35 259, 280, 301, 303, 344, 346, Voltage dependent Na+ channel (VDNa), 162 352, 498–499, 618, 625–646, Voltage-gated Ca2+ channels (VGCC), 641, 693–694, 789, 792–793, 158–164, 196, 574–575, 574f, 795–799, 853, 867, 892, 930, 707–708, 712, 717–719, 750, 950 765, 795, 799, 824, 832, 833f, Williamson, S. M., 359–368 836–837 Wilms’ tumours, 939 Voltage-gated ion channels, 168, 214, 390, Wind-up activity, 604 518–519 Wistar Kyoto control rat, 179 Voltage-operated Ca2+ channel (VOCC), 362, Wistar-Kyoto rats, 789 669 Wistar Kyoto VSMC, 179 Voltage-operated calcium channel (VOC), 688, With No lysine (K) (WNK), 256 698 kinase 1, 256 Voltage sensong domain (VSD), 519 kinase 4, 256 Vomeronasal organ (VNO), 127–129 WNK, see With No lysine (K) (WNK) input resistance, 127 WNK4, 255t, 257, 561 vonEuler,U.S.,802 Wnk4D561A/+ knock-in mouse model, 257 Voolstra, O., 566 Wolstenholme, A. J., 359–368 VR1, see Vanilloid receptor subtype 1 (VR1) Wong, C. O., 789–774 VRL-1, see Vanilloid-receptor-like protein 1 Wood, W. B., 324 (VRL-1) Wortmannin, 399, 402, 404 VR1 receptors, 127, 653, 839 W. stuhlmannii (warburganal), 46t, 52 VR2 receptors, 127 WT, see Wild-type (WT) VSD, see Voltage sensong domain (VSD) Wu, G., 263 Index 1095

Wu, X., 577 TRPP2 homologs in other yeast, 319 Wyeth, 654 TRPP2 homologs in S. cerevisiae, Wyman, J., 481–482 319–320 Yvc1 homologs in other yeast, 318 X vacuolar channel, mechanosensation of, Xanthium catharticum (ziniolide), 47t, 52 317 Xenobiotic-induced liver toxicity, 676 Yvc1 homologs in other, 318 Xenopus embryogenesis, TRPC1 in axon path Yeast episomal plasmids (Yeps), 29 during, 343–344 Yeast integrating plasmids (Yips), 29 L-type voltage-dependent calcium Yellow mustard, 66 channels, 343 Yeps, see Yeast episomal plasmids (Yeps) netrin-1, 344 Yersiniae, 453 NMR exchange spectroscopy, 344 Yips, see Yeast integrating plasmids (Yips) patch-clamp recordings, 343 Y745 residues, 186, 481 PPIase activity, 344 Y511/S512 motif, 61 Xenopus laevis oocytes, 240, 297–298, 918 Yuan, X. J., 423 Xenopus oocytes, 17, 53, 254, 256, 258, 261, Yu, P. C., 347 343, 349, 506, 556, 561–562, Yu, Y., 1–19 564, 799, 888, 1021 Yvc1 channel, function of, 317 Xenopus tropicalis, 221–222, 351 Xestospongin C, 92 Z Xhu, L., 93 Zaccai, Dr. G., 461, 462 Xia, R., 637–656 Zaccai, J., 461, 464 Xiao, R., 323–333 Zanthoxylum piperitum (Szechuan pepper), X-ray crystallography, 2–3, 5–7, 10, 19, 32–33 68t, 69 TRPV1, ARD structure, 12 Zavitsanou, K., 1000 TRPV2, ARD structure, 12 Zebraﬁsh (Danio rerio), 244, 296, 329, TRPV4, ARD structure, 12 341–352, 638, 671t–672t, 677, TRPV6, ARD structure, 12 761t–762t, 768, 1015 Xu, X. Z. S., 323–333 Zhang, W., 244, 264, 531–540 Zhang, X., 678 Y Zhang, Z., 244 Y555, 61 Zheng, Y.-M., 731–742 Yang, F., 478, 524–525 Zholos, A., 707–723 Yang, J., 1–19 Zholos, T., 723 Yang, X. R., 719 Zhu, M. X., 126 Yao, J. F., 502 Zingerone, 45t, 50 Yao, X., 759–775 Zingiberaceae, 51 Yasuo Mori, 96, 373–383 Zingiber mioga (miogadial/miogatrial), 46t, Yeast, 241 52, 68t TRP channels in, 315–320 Zingiber ofﬁcinale, 45t, 50–51 function of the Yvc1 channel, 317 Ziniolide, 47t, 52 mechanosensation of, 317 Zona pellucida (ZP3), 126, 130, 301, 882, microbial ion channels, 315–316 892–893 molecular dissection of YVC1 ZP3, see Zona pellucida (ZP3) (TRPY1), 318 ZP3 glycoprotein, 130 S. cerevisiae TRP channels, 316–317 ZP3-induced calcium entry, 126 TRP homologs in S. pombe, 318–319 Zucker, K., 823