Index

A double-pulse protocol, 137–138 A-1048400, 41–42 L-type Ca2+ channels on/off cytoplasmic Absence epilepsy membrane, 139–140 definition, 95 pancreatic ß-cells, 137–138 genetics of, 101–103 reversible regulation of L-type Ca2+, low-voltage threshold 142–143 antiseizure , 101 T-Type Ca2+ channel upregulation Cacna1a gene, 99 hypothesis, 143–144 Cacna1h gene, 103–105 two-phase process, 141 GAERS, 98–99 window current, 139 genetically modified mice, 100–101 , 38, 39 spike–wave discharge, 97–98 B2(2)-M17 cell line, 57 Adenosine triphosphate (ATP), 28 Aldosterone/angiotensin system, 23 2-(1-Alkylpiperidin-4-yl)-N-[(1 R)-1- C (4-Fluorophenyl)-2-Methylpropyl] Ca2+/calmodulin-dependent kinase II acetamide derivatives, 44 (CaMKII), 29 Alpha 1G (Cacna1g, Cav3.1), 100 Cacna1a gene, 99 Alpha 1I (Cav3.3), 104 Cacna1g (alpha 1G) gene, 103 Anandamide, 24 Cacna1h gene, 102–105 Angiotensin II (Ang II), 73–76 Cacna1i gene, 103 , 24 Calcineurin-NFAT hypertrophic pathways Arrhythmias angiotensin II and norepinephrine, 73–75 atrial fibrillation, 86–87 pathological hypertrophy, 76 diastolic depolarization Calcium signaling, 112, 118 atrioventricular nodal cells, 86 Calmodulin, 113 ionic currents, 83–84 cAMP-Epac signaling pathway, 28 L-type Ca2+ channel, 84–85 Cancer cell proliferation T-type Ca2+ channel, 85–86 breast cancer, 117–118 Atrial fibrillation, 86–87 calcium signaling, 118 Atrioventricular (AV) nodal cells, 86 cyclophosphamide, 118 Autism spectrum disorder (ASD), 10–11 esophageal carcinoma, 119 GLUTs, 116 intracranial tumors, 118 B and , 117 Basal insulin release mRNA and protein, 116 2+ basal [Ca ]i, values of, 138 prostate cancer, 118–119 biophysical kinetics, 140–141 Cardiac hypertrophy, 9 chronic high glucose, 136–137 heart failure, 73–76

# Springer-Verlag Wien 2015 151 S.W. Schaffer, M. Li (eds.), T-type Calcium Channels in Basic and Clinical Science, DOI 10.1007/978-3-7091-1413-1 152 Index

Cardiac hypertrophy (cont.) G myocardial hypertrophy, 73–76 Genetic absence epileptic rats from Strasbourg pathological development, 76–78 (GAERS), 98–99 physiological roles, 71–72 Glucose, 20–21 Cav3.1 (α1G), 72–73 G-protein-coupled receptor (GPCR), 26 Cav3.2 (α 1H), 72 Ca 3.2 knockout (KO) mice, 100 v H Cav3.3 knockout (KO) mice, 100–101 Cell proliferation, 114–116 Heart failure definition, 73 calcium and, 111–114 2+ MCF-7 and MCF-10A, 114 T-type Ca channel, 73–76 Chemotherapy, 119–121 Hyperpolarization-activated cyclic nucleotide- Childhood absence epilepsy (CAE) gated (HCN) channel, 84 Cacna1g and Cacna1i, 103 , 9 Cacna1h gene, 102–103 Hypertrophic cardiomyopathy, 20 characteristics of, 102 CREB hypertrophic pathways, 73–75 I Cyclophosphamide, 118 Idiopathic generalized epilepsy (IGE), 102–103 Cytosolic calcium, 61 IK-decay hypothesis, 84 Inflammatory cytokines interferin-γ (IFN-γ), 21 Insulin like growth factor-I (IGF-I), 23–24 D Intercellular signals Diastolic depolarization, 85–86 anandamide, 24 atrial fibrillation, 86–87 cytokines, 21–22 atrioventricular nodal cells, 86 glucose, 20–21 ionic currents, 83–84 2+ hormones L-type Ca channel, 84–85 aldosterone/angiotensin system, 23 3,5-dichloro-N-[1-(2,2-dimethyl-tetrahydro- estrogens, 22–23 pyran-4-ylmethyl)-4-fluoro- IGF-I, 23–24 piperidin-4-ylmethyl]-benzamide testosterone, 22 (TTA-P2), 130 nitric oxide/nitrous oxide, 24–25 Dithiothreitol (DTT), 105 zinc, 25–26 Interleukin-1 (IL-1β), 21 Intracellular signaling pathway E ATP, 28 E-cadherin, 114 CaMKII, 29 , 38, 39 cAMP and protein kinase A, 28–29 Embryonic stem (ES) cells, 57–58 heterotrimeric G-protein, 26 Endocannabinoids, 24 protein kinase C, 27 Epilepsy, 10–11 Rho-associated kinase, 26–27 Epoxyeicosatrienoic acids (EETs), 24 transcription factors, 30 , 39–40 tyrosine kinase, 29–30 Estrogen, 22–23 Irritable bowel syndrome (IBS), 130 (ETX) Ischemia-reperfusion injury, 87–90. See also absence seizures, 101 Cardiac hypertrophy chemical structures, 39–40 pain management, 129 K

KATP channel-dependent mechanism, 141 F KST-5468, 43–44 Funny current (If), 84 KYS05090, 43, 44 Index 153

L O Ligand lysophosphatidic acid (LPA), 26–27 Oligodeoxynucleotides, 129 LNCaP prostate cancer cell line, 53–55, 58 Oncomodulin, 114 L-type Ca2+ channel, 64 arrhythmia, 86–87 atrial fibrillation, 86–87 P diastolic depolarization, 84–85 PACAP. See Pituitary adenylate cyclase neuroendocrine differentiation, 64 activating polypeptide (PACAP) Pacemaker cells, 83–84 Pain management M Cav3.2 channels, 128–129 Metabotropic glutamate receptor (mGluR1), 115 diabetic neuropathy, 130 Mibefradil irritable bowel syndrome, 130 and hypertension, 7–8 neuropathic pain, 129–130 cancer cell proliferation, 117 nociception, 128–129 chemical structures, 38 nomenclature of calcium channels, 128 clinical development, 40 type 2 diabetes mellitus, 131 ischemia–reperfusion injury, 88–89 Pancreatic ß-cells, 137–138 pain management, 129 PC12 cell line, 53 , 39–40 Pimozide, 117 N Pituitary adenylate cyclase activating Neuroendocrine (NE) differentiation polypeptide (PACAP), 53 calcium homeostasis alteration, 54–56 Prostate cancer, NE differentiation, 64–65 cancer progression, 64–65 Protein kinase A (PKA), 28–29 cell models, 53–54 Protein kinase C (PKC), 27 features of, 52–53 Pulmonary artery smooth muscle cell in LNCaP cells, 54, 55 (PASMC), 23 L-type stimulation, 64 Purkinje cells, 86 putative signalling mechanisms, 63 signalling pathways, 54, 55 T-type calcium channels R hormone/neurohormone secretion, 61–62 R(–)-efonidipine, 45 molecular expression, 59, 60 Reticular thalamic (RT) neurons neuritic extension, 59–61 alpha 1H (Cav3.2), 104 voltage-dependent calcium channels alpha 1I (Cav3.3), 104 cell lines, 58 in early sleep, 98 classification, 56 Retinoblastoma Y-79 cell line, 57 embryonic stem cells, 57–58 Rho-associated kinase (ROCK), 26–27 neuroblastoma cell lines, 56–57 retinoblastoma cells, 57 Neuropathic pain S Cav3.2, role of, 130 Selenoprotein T (SelT), 56 T-type channels role in, 11–12 Sleep disturbances, 10–11 NG108-15 cell line, 56–57, 61 SN56 cells, 57 Nickel chloride, 137–138 Spike-wave discharges (SWD), 97–98, 101 Nitric oxide (NO), 24–25 Nitrous oxide (N2O), 24–25 NNC-55-0396, 43, 45–46, 118, 120 T Nociception, 128–129 Tamoxifen, 120 Norepinephrine, 73–76 Testosterone, 22 N-[[1-[2-(Tert-Butylcarbamoylamino)Ethyl]-4- TRPC cation channels, 75–76 (Hydroxymethyl)-4-Piperidyl] TTA-A2, 41–43 Methyl]-3,5-Dichloro-Benzamide, 45 TTA-P2, 41–43 154 Index

T-type calcium channel (TCC) TTA-A2, TTA-P2, 42–43 antiepilepsy agents, 39–40 secretion and exocytosis, 8 antiseizure drugs and, 101 sleep disturbances and epilepsy, 10–11 arrhythmia, 86–87 steady-state voltage properties, 7 atrial fibrillation, 86–87 structural features, 3–5 autism spectrum disorders, 10–11 Tumor necrosis factor-α (TNF-α), 21 cardiac hypertrophy Type 1 diabetes mellitus heart failure, 73–76 inflammatory cytokines interferin-γ,21 myocardial hypertrophy, 73–76 interleukin-1, 21 pathological development, 76–78 tumor necrosis factor-α,21 physiological roles, 71–72 Type 2 diabetes mellitus, 131 Cav channels, 4 Tyrosine kinase, 29–30 cell division and cancer, 9 cellular excitability regulation, 6–7 clinical development V mibefradil (redevelopment), 40 sodium, 39–40 Z-944, 40–41 , 88 dihydropyridine derivatives, 39 Voltage-dependent calcium channel, NE hypertension and cardiac hypertrophy, 9 differentiation membrane topology, 4 cell lines, 58 mibefradil, 38–39 classification, 56 in myocyte contraction and tone, 8 embryonic stem cells, 57–58 neuropathic pain, 11–12 neuroblastoma cell lines, 56–57 pharmacology, 7–8 retinoblastoma cells, 57 preclinical research A-1048400, 41–42 KST-5468, 43–44 Z KYS05090, 43, 44 Z-944, 40–41 mibefradil derivatives, 45–46 Zinc, 25–26 R (–)-efonidipine, 45 , 39–40