DOCSLIB.ORG

TRP Channels of Intracellular Membranes

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
TRP Channels of Intracellular Membranes JOURNAL OF NEUROCHEMISTRY | 2010 | 113 | 313–328 doi: 10.1111/j.1471-4159.2010.06626.x The Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, Michigan, USA Abstract potential (TRP) proteins are a superfamily (28 members in Ion channels are classically understood to regulate the flux of mammal) of Ca2+-permeable channels with diverse tissue ions across the plasma membrane in response to a variety of distribution, subcellular localization, and physiological func- environmental and intracellular cues. Ion channels serve a tions. Almost all mammalian TRP channels studied thus far, number of functions in intracellular membranes as well. These like their ancestor yeast TRP channel (TRPY1) that localizes channels may be temporarily localized to intracellular mem- to the vacuole compartment, are also (in addition to their branes as a function of their biosynthetic or secretory path- plasma membrane localization) found to be localized to ways, i.e., en route to their destination location. Intracellular intracellular membranes. Accumulated evidence suggests membrane ion channels may also be located in the endocytic that intracellularly-localized TRP channels actively participate pathways, either being recycled back to the plasma mem- in regulating membrane traffic, signal transduction, and brane or targeted to the lysosome for degradation. Several vesicular ion homeostasis. This review aims to provide a channels do participate in intracellular signal transduction; the summary of these recent works. The discussion will also be most well known example is the inositol 1,4,5-trisphosphate extended to the basic membrane and electrical properties of receptor (IP3R) in the endoplasmic reticulum. Some organellar the TRP-residing compartments. intracellular membrane channels are required for the ionic Keywords: endosomes, intracellular channel, lysosomes, homeostasis of their residing organelles. Several newly-dis- membrane traffic, TRP channel, TRPML. covered intracellular membrane Ca2+ channels actually play J. Neurochem. (2010) 113, 313–328. active roles in membrane trafficking. Transient receptor TRPs) are activated by a variety of environmental cues such TRP channels and organelles as temperature, mechanical force, and plant-derived volatiles (reviewed in Refs. Clapham 2003; Montell 2005; Nilius Overview of TRP channels et al. 2007). Many of the sensory TRPs, along with the Transient receptor potential (TRP) is a cation channel superfamily with diverse physiological functions including thermosensation and mechanosensation (excellently re- Received January 17, 2010; accepted January 25, 2010. Address correspondence and reprint requests to Haoxing Xu, The viewed in Refs. Clapham 2003; Montell 2005; Nilius et al. Department of Molecular, Cellular, and Developmental Biology, Uni- 2007). Mammalian TRPs can be divided into six subfamilies: versity of Michigan, 3089 Natural Science Building (Kraus), 830 North TRPC(1–7), TRPV(1–6), TRPM(1–8), TRPA(1), TRPP(1– University, Ann Arbor, MI 48109, USA. E-mail: [email protected] 3), and TRPML(1–3) (Fig. 1). In past years, extensive efforts Abbreviations used: AM, acetoxymethyl; BAPTA, 1,2-bis(2-amino- have been made to elucidate three basic aspects of TRP phenoxy)ethane-N,N,N¢,N¢-tetraacetic acid; CaM, Calmodulin; CICR, Ca2+-induced Ca2+ release; EPSP, excitatory postsynaptic potential; ER, channels: the channel pore properties, the activation (gating) endoplasmic reticulum; IP3R, inositol 1,4,5-trisphosphate receptor; LEL, mechanisms, and the channels’ subcellular localization. Of late endosomal and lysosomal; LROs, lysosome-related organelles; these, the biophysical properties of the TRP channel pore MHCII, major histocompatibility complex II; ML4, type IV mucolipi- have been best characterized. When activated, most TRPs dosis; NAADP, nicotinic acid adenine dinucleotide phosphate; PIP, conduct Ca2+, as well as Na+ and K+ ions. The activation/ phosphoinositide; PM, plasma membrane; RyR, ryanodine receptor; SG, secretory granule; SNARE, soluble NSF attachment protein receptors; gating mechanisms, however, have not been described in SR, sarcoplasmic reticulum; SV, secretory vesicle; SyV, synaptic vesicle; detail for most TRPs. In sensory cells such as somatosensory TG, thapsigargin; TGN, trans-Golgi network; TRP, transient receptor neurons, a subset of TRP channels (so-called ‘sensory’ potential. Ó 2010 The Authors Journal Compilation Ó 2010 International Society for Neurochemistry, J. Neurochem. (2010) 113, 313–328 313 314 | X.-P. Dong et al. C2 C7 C6 A1(Icilin) C3 V V V1(H+ ?, Capsaicin) C5 G V2 C4 ER or G ([Cl - ] , H+ ) V V lumen SV/SG EE V4 (Osmolarity ) C1 ? Fig. 1 Intracellular location and putative V3 activation mechanisms of TRP channels. TRPs can be divided into six groups V5 (TRPC, TRPV, TRPM, TRPA, TRPML, and RE TRPP). TRPML1-3, TRPV2, and TRPY1 M5 V6 (yeast TRP yvc1), and TRPM7 (in red) are likely to play active roles in membrane M4 traffic and exocytosis. TRPM2, TRPM8, ER ER TRPV1, TRPP1, TRPA1, and TRPV4 (in M8 LEL LEL 2+ P1([Ca ] i) (Cold/menthol) green) have been shown to be active in M2 V intracellular membranes and may play roles (ADPR, NAADP?) P2 SyV LY in intracellular signal transduction. TRPC3- P3 M7 V 6, TRPMV5/6, TRPM1, TRPM7, and EE TRPML2/3 (in blue) have been shown to M6 RE M3 M1 ML1 undergo regulated exocytosis. Intracellular ML3 Y1 ML2 localization of other TRPs (in black) has not (Mechanical force, [Ca 2+ ] ) i been well documented. non-sensory TRPs, are also expressed in non-sensory tissues. Ramsey et al. 2006). It is not known if vesicular intracellular Here the endogenous cellular cues activating the TRPs are membrane TRPs are modulated by these same signaling largely unknown, although ligands of the G protein-coupled molecules. It is also not known whether intracellular receptor and RTK (receptor tyrosine kinase) families report- membrane TRPs are modulated by luminal factors. Given edly activate or modulate TRPs in heterologous systems that the chemicophysical properties of intracellular mem- (reviewed in Ref. Ramsey et al. 2006). Initially thought to be branes differ significantly from those of the plasma mem- solely plasma membrane (PM) channels mediating Ca2+ brane (Watson and Pessin 2001), it is of interest whether entry, almost all mammalian TRPs studied thus far have also vesicular TRPs function in the secretory/endocytic pathways been found to be localized to intracellular vesicular mem- in a similar fashion to their plasma membrane counterparts. branes (Turner et al. 2003; Bezzerides et al. 2004; Krapi- In this review, we will mainly discuss TRP channels whose vinsky et al. 2006; Dong et al. 2008; Lange et al. 2009). residing compartments have been reasonably defined, espe- Despite the fact that TRP channel activity can be recorded in cially those for whom channel activities have been measured the plasma membrane using functional assays, and that TRP in their residing compartments. proteins can be detected in the plasma membrane using surface labeling techniques, the majority of heterologously- Overview of intracellular organelles expressed and many of the endogenous TRP proteins are In most mammalian cells there are at least eight different located intracellularly (for example see Refs Turner et al. types of intracellular organelles, which can be arbitrarily 2003; Bezzerides et al. 2004; Krapivinsky et al. 2006; Dong divided into two groups (Michelangeli et al. 2005). The first et al. 2008; Lange et al. 2009; Oancea et al. 2009). The endocytic, secretory and autophagic group (group I) includes molecular identities of these intracellular TRP-residing the endoplasmic reticulum (ER), the Golgi apparatus, compartments are poorly defined. It remains unclear whether secretory vesicles/granules, endosomes, autophagosomes, TRPs appear in these compartments as intermediates of and lysosomes (see Fig. 2). These group I organelles biosynthetic pathways being shuttled to their ultimate exchange materials with each other, either directly by destinations, or if they are active participants in signal complete or partial (‘kiss and run’) membrane fusion, or transduction and/or membrane trafficking. If the latter is true, with the aid of intermediate transport vesicles that bud off the larger question arises as to how TRPs function in vesicles (membrane fission) from the donor membrane and migrate to and are activated and/or modulated by cellular cues. TRPs the target membrane (Piper and Luzio 2004; Roth 2004; localized to the plasma membrane (PM TRPs) are modulated Luzio et al. 2007b; Stenmark 2009). In specialized cell by G protein signaling, lipid signaling, and protein phos- types, there are also cell-type-specific vesicular compart- phorylation and de-phosphorylation events (Clapham 2003; ments derived from endocytic and secretory pathways. For Ó 2010 The Authors Journal Compilation Ó 2010 International Society for Neurochemistry, J. Neurochem. (2010) 113, 313–328 TRP calcium channels in intracellular organelles | 315 example melanosomes, which release melanin in response to 2007). Evidence now exists, however, suggesting that light, are specialized lysosome-related organelles (LROs) in intracellular traffic is also highly regulated. The final trigger melanocytes (Blott and Griffiths 2002). In neurons, synaptic of intracellular membrane fusion is also likely to be a rise of 2+ vesicles that release neurotransmitters upon electrochemical [Ca ]cyt, whose amplitude and duration might be in a scale stimulation are derived from endosomes
Load more

Recommended publications
  • A Computational Model of Large Conductance Voltage and Calcium
    Journal of Computational Neuroscience (2019) 46:233–256 https://doi.org/10.1007/s10827-019-00713-9 A computational model of large conductance voltage and calcium activated potassium channels: implications for calcium dynamics and electrophysiology in detrusor smooth muscle cells Suranjana Gupta1 · Rohit Manchanda1 Received: 11 September 2018 / Revised: 14 February 2019 / Accepted: 19 February 2019 / Published online: 25 April 2019 © Springer Science+Business Media, LLC, part of Springer Nature 2019 Abstract The large conductance voltage and calcium activated potassium (BK) channels play a crucial role in regulating the excitability of detrusor smooth muscle, which lines the wall of the urinary bladder. These channels have been widely characterized in terms of their molecular structure, pharmacology and electrophysiology. They control the repolarising and hyperpolarising phases of the action potential, thereby regulating the firing frequency and contraction profiles of the smooth muscle. Several groups have reported varied profiles of BK currents and I-V curves under similar experimental conditions. However, no single computational model has been able to reconcile these apparent discrepancies. In view of the channels’ physiological importance, it is imperative to understand their mechanistic underpinnings so that a realistic model can be created. This paper presents a computational model of the BK channel, based on the Hodgkin-Huxley formalism, constructed by utilising three activation processes — membrane potential, calcium inflow from voltage-gated calcium channels on the membrane and calcium released from the ryanodine receptors present on the sarcoplasmic reticulum. In our model, we attribute the discrepant profiles to the underlying cytosolic calcium received by the channel during its activation. The model enables us to make heuristic predictions regarding the nature of the sub-membrane calcium dynamics underlying the BK channel’s activation.
    [Show full text]
  • Entropy-Based Regulation of Cluster Ion Channel Density
    www.nature.com/scientificreports OPEN Molecular and cellular correlates in Kv channel clustering: entropy‑based regulation of cluster ion channel density Limor Lewin1, Esraa Nsasra1, Ella Golbary1, Uzi Hadad2, Irit Orr1 & Ofer Yifrach1* Scafold protein-mediated ion channel clustering at unique membrane sites is important for electrical signaling. Yet, the mechanism(s) by which scafold protein-ion channel interactions lead to channel clustering or how cluster ion channel density is regulated is mostly not known. The voltage‑activated potassium channel (Kv) represents an excellent model to address these questions as the mechanism underlying its interaction with the post-synaptic density 95 (PSD-95) scafold protein is known to be controlled by the length of the extended ‘ball and chain’ sequence comprising the C-terminal channel region. Here, using sub-difraction high-resolution imaging microscopy, we show that Kv channel ‘chain’ length regulates Kv channel density with a ‘bell’-shaped dependence, refecting a balance between thermodynamic considerations controlling ‘chain’ recruitment by PSD-95 and steric hindrance due to the spatial proximity of multiple channel molecules. Our results thus reveal an entropy‑based mode of channel cluster density regulation that mirrors the entropy‑based regulation of the Kv channel-PSD-95 interaction. The implications of these fndings for electrical signaling are discussed. Action potential generation, propagation and the evoked synaptic potential all rely on precisely timed events associated with activation and inactivation gating transitions of voltage-dependent Na + and K + channels, clus- tered in multiple copies at unique membrane sites, such as the initial segment of an axon, nodes of Ranvier, pre-synaptic terminals or at the post-synaptic density (PSD)1–3.
    [Show full text]
  • Transient Receptor Potential (TRP) Channels in Haematological Malignancies: an Update
    biomolecules Review Transient Receptor Potential (TRP) Channels in Haematological Malignancies: An Update Federica Maggi 1,2 , Maria Beatrice Morelli 2 , Massimo Nabissi 2 , Oliviero Marinelli 2 , Laura Zeppa 2, Cristina Aguzzi 2, Giorgio Santoni 2 and Consuelo Amantini 3,* 1 Department of Molecular Medicine, Sapienza University, 00185 Rome, Italy; [email protected] 2 Immunopathology Laboratory, School of Pharmacy, University of Camerino, 62032 Camerino, Italy; [email protected] (M.B.M.); [email protected] (M.N.); [email protected] (O.M.); [email protected] (L.Z.); [email protected] (C.A.); [email protected] (G.S.) 3 Immunopathology Laboratory, School of Biosciences and Veterinary Medicine, University of Camerino, 62032 Camerino, Italy * Correspondence: [email protected]; Tel.: +30-0737403312 Abstract: Transient receptor potential (TRP) channels are improving their importance in differ- ent cancers, becoming suitable as promising candidates for precision medicine. Their important contribution in calcium trafficking inside and outside cells is coming to light from many papers published so far. Encouraging results on the correlation between TRP and overall survival (OS) and progression-free survival (PFS) in cancer patients are available, and there are as many promising data from in vitro studies. For what concerns haematological malignancy, the role of TRPs is still not elucidated, and data regarding TRP channel expression have demonstrated great variability throughout blood cancer so far. Thus, the aim of this review is to highlight the most recent findings Citation: Maggi, F.; Morelli, M.B.; on TRP channels in leukaemia and lymphoma, demonstrating their important contribution in the Nabissi, M.; Marinelli, O.; Zeppa, L.; perspective of personalised therapies.
    [Show full text]
  • Snapshot: Mammalian TRP Channels David E
    SnapShot: Mammalian TRP Channels David E. Clapham HHMI, Children’s Hospital, Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA TRP Activators Inhibitors Putative Interacting Proteins Proposed Functions Activation potentiated by PLC pathways Gd, La TRPC4, TRPC5, calmodulin, TRPC3, Homodimer is a purported stretch-sensitive ion channel; form C1 TRPP1, IP3Rs, caveolin-1, PMCA heteromeric ion channels with TRPC4 or TRPC5 in neurons -/- Pheromone receptor mechanism? Calmodulin, IP3R3, Enkurin, TRPC6 TRPC2 mice respond abnormally to urine-based olfactory C2 cues; pheromone sensing 2+ Diacylglycerol, [Ca ]I, activation potentiated BTP2, flufenamate, Gd, La TRPC1, calmodulin, PLCβ, PLCγ, IP3R, Potential role in vasoregulation and airway regulation C3 by PLC pathways RyR, SERCA, caveolin-1, αSNAP, NCX1 La (100 µM), calmidazolium, activation [Ca2+] , 2-APB, niflumic acid, TRPC1, TRPC5, calmodulin, PLCβ, TRPC4-/- mice have abnormalities in endothelial-based vessel C4 i potentiated by PLC pathways DIDS, La (mM) NHERF1, IP3R permeability La (100 µM), activation potentiated by PLC 2-APB, flufenamate, La (mM) TRPC1, TRPC4, calmodulin, PLCβ, No phenotype yet reported in TRPC5-/- mice; potentially C5 pathways, nitric oxide NHERF1/2, ZO-1, IP3R regulates growth cones and neurite extension 2+ Diacylglycerol, [Ca ]I, 20-HETE, activation 2-APB, amiloride, Cd, La, Gd Calmodulin, TRPC3, TRPC7, FKBP12 Missense mutation in human focal segmental glomerulo- C6 potentiated by PLC pathways sclerosis (FSGS); abnormal vasoregulation in TRPC6-/-
    [Show full text]
  • Modeling of Voltage-Gated Ion Channels
    Modeling of voltage-gated ion channels Modeling of voltage-gated ion channels Pär Bjelkmar c Pär Bjelkmar, Stockholm 2011, pages 1-65 Cover picture: Produced by Pär Bjelkmar and Jyrki Hokkanen at CSC - IT Center for Science, Finland. Cover of PLoS Computational Biology February 2009 issue. ISBN 978-91-7447-336-0 Printed in Sweden by US-AB, Stockholm 2011 Distributor: Department of Biochemistry and Biophysics, Stockholm University Abstract The recent determination of several crystal structures of voltage-gated ion channels has catalyzed computational efforts of studying these re- markable molecular machines that are able to conduct ions across bi- ological membranes at extremely high rates without compromising the ion selectivity. Starting from the open crystal structures, we have studied the gating mechanism of these channels by molecular modeling techniques. Firstly, by applying a membrane potential, initial stages of the closing of the channel were captured, manifested in a secondary-structure change in the voltage-sensor. In a follow-up study, we found that the energetic cost of translocating this 310-helix was significantly lower than in the origi- nal conformation. Thirdly, collaborators of ours identified new molecular constraints for different states along the gating pathway. We used those to build new protein models that were evaluated by simulations. All these results point to a gating mechanism where the S4 helix undergoes a secondary structure transformation during gating. These simulations also provide information about how the protein in- teracts with the surrounding membrane. In particular, we found that lipid molecules close to the protein diffuse together with it, forming a large dynamic lipid-protein cluster.
    [Show full text]
  • Stem Cells and Ion Channels
    Stem Cells International Stem Cells and Ion Channels Guest Editors: Stefan Liebau, Alexander Kleger, Michael Levin, and Shan Ping Yu Stem Cells and Ion Channels Stem Cells International Stem Cells and Ion Channels Guest Editors: Stefan Liebau, Alexander Kleger, Michael Levin, and Shan Ping Yu Copyright © 2013 Hindawi Publishing Corporation. All rights reserved. This is a special issue published in “Stem Cells International.” All articles are open access articles distributed under the Creative Com- mons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Editorial Board Nadire N. Ali, UK Joseph Itskovitz-Eldor, Israel Pranela Rameshwar, USA Anthony Atala, USA Pavla Jendelova, Czech Republic Hannele T. Ruohola-Baker, USA Nissim Benvenisty, Israel Arne Jensen, Germany D. S. Sakaguchi, USA Kenneth Boheler, USA Sue Kimber, UK Paul R. Sanberg, USA Dominique Bonnet, UK Mark D. Kirk, USA Paul T. Sharpe, UK B. Bunnell, USA Gary E. Lyons, USA Ashok Shetty, USA Kevin D. Bunting, USA Athanasios Mantalaris, UK Igor Slukvin, USA Richard K. Burt, USA Pilar Martin-Duque, Spain Ann Steele, USA Gerald A. Colvin, USA EvaMezey,USA Alexander Storch, Germany Stephen Dalton, USA Karim Nayernia, UK Marc Turner, UK Leonard M. Eisenberg, USA K. Sue O’Shea, USA Su-Chun Zhang, USA Marina Emborg, USA J. Parent, USA Weian Zhao, USA Josef Fulka, Czech Republic Bruno Peault, USA Joel C. Glover, Norway Stefan Przyborski, UK Contents Stem Cells and Ion Channels, Stefan Liebau,
    [Show full text]
  • Download File
    STRUCTURAL AND FUNCTIONAL STUDIES OF TRPML1 AND TRPP2 Nicole Marie Benvin Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Graduate School of Arts and Sciences COLUMBIA UNIVERSITY 2017 © 2017 Nicole Marie Benvin All Rights Reserved ABSTRACT Structural and Functional Studies of TRPML1 and TRPP2 Nicole Marie Benvin In recent years, the determination of several high-resolution structures of transient receptor potential (TRP) channels has led to significant progress within this field. The primary focus of this dissertation is to elucidate the structural characterization of TRPML1 and TRPP2. Mutations in TRPML1 cause mucolipidosis type IV (MLIV), a rare neurodegenerative lysosomal storage disorder. We determined the first high-resolution crystal structures of the human TRPML1 I-II linker domain using X-ray crystallography at pH 4.5, pH 6.0, and pH 7.5. These structures revealed a tetramer with a highly electronegative central pore which plays a role in the dual Ca2+/pH regulation of TRPML1. Notably, these physiologically relevant structures of the I-II linker domain harbor three MLIV-causing mutations. Our findings suggest that these pathogenic mutations destabilize not only the tetrameric structure of the I-II linker, but also the overall architecture of full-length TRPML1. In addition, TRPML1 proteins containing MLIV- causing mutations mislocalized in the cell when imaged by confocal fluorescence microscopy. Mutations in TRPP2 cause autosomal dominant polycystic kidney disease (ADPKD). Since novel technological advances in single-particle cryo-electron microscopy have now enabled the determination of high-resolution membrane protein structures, we set out to solve the structure of TRPP2 using this technique.
    [Show full text]
  • TRPM7 Facilitates Cholinergic Vesicle Fusion with the Plasma Membrane
    TRPM7 facilitates cholinergic vesicle fusion with the plasma membrane Sebastian Brauchi*, Grigory Krapivinsky, Luba Krapivinsky, and David E. Clapham† Department of Cardiology, Howard Hughes Medical Institute, Children’s Hospital Boston, and Department of Neurobiology, Harvard Medical School, Enders Building 1309, 320 Longwood Avenue, Boston, MA 02115 Contributed by David E. Clapham, January 29, 2008 (sent for review December 3, 2007) TRPM7, of the transient receptor potential (TRP) family, is both an the inclusion of a zinc-finger domain (13). This kinase phos- ion channel and a kinase. Previously, we showed that TRPM7 is phorylates TRPM7 (14) and other substrates [e.g., annexin 1 (15) located in the membranes of acetylcholine (ACh)-secreting synaptic and myosin heavy chain (16)], but its physiological role is not vesicles of sympathetic neurons, forms a molecular complex with known. The pore of TRPM7 was proposed to be a major entry proteins of the vesicular fusion machinery, and is critical for mechanism for Mg2ϩ ions and, in this role, critical for cell stimulated neurotransmitter release. Here, we targeted pHluorin survival (17). TRPM7 is localized in the membrane of sympa- to small synaptic-like vesicles (SSLV) in PC12 cells and demonstrate thetic neuronal acetylcholine (ACh)-secreting synaptic vesicles that it can serve as a single-vesicle plasma membrane fusion as part of a molecular complex of synaptic vesicle-specific reporter. In PC12 cells, as in sympathetic neurons, TRPM7 is located proteins and its permeability is critical
    [Show full text]
  • The Role of TRP Proteins in Mast Cells
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE REVIEW ARTICLE published: 12 Juneprovided 2012 by Frontiers - Publisher Connector doi: 10.3389/fimmu.2012.00150 The role ofTRP proteins in mast cells Marc Freichel*, Julia Almering and VolodymyrTsvilovskyy Pharmakologisches Institut, Universität Heidelberg, Heidelberg, Germany Edited by: Transient receptor potential (TRP) proteins form cation channels that are regulated through Ulrich Blank, Université Paris-Diderot strikingly diverse mechanisms including multiple cell surface receptors, changes in tem- Paris 7, France 2+ 2+ perature, in pH and osmolarity, in cytosolic free Ca concentration ([Ca ]i), and by Reviewed by: Marc Benhamou, Institut National de phosphoinositides which makes them polymodal sensors for fine tuning of many cellu- la Santé et de la Recherche Médicale, lar and systemic processes in the body. The 28 TRP proteins identified in mammals are France classified into six subfamilies: TRPC, TRPV, TRPM, TRPA, TRPML, and TRPP.When acti- Pierre Launay, Institut National de la vated, they contribute to cell depolarization and Ca2+ entry. In mast cells, the increase of Santé et de la Recherche Médicale, 2+ 2+ France [Ca ]i is fundamental for their biological activity, and several entry pathways for Ca and 2+ 2+ *Correspondence: other cations were described including Ca release activated Ca (CRAC) channels. Like 2+ Marc Freichel, Pharmakologisches in other non-excitable cells, TRP channels could directly contribute to Ca influx via the Institut, Universität Heidelberg, Im plasma membrane as constituents of Ca2+ conducting channel complexes or indirectly by Neuenheimer Feld 366, 69120 shifting the membrane potential and regulation of the driving force for Ca2+ entry through Heidelberg, Germany.
    [Show full text]
  • Supplementary Table 2
    Supplementary Table 2. Differentially Expressed Genes following Sham treatment relative to Untreated Controls Fold Change Accession Name Symbol 3 h 12 h NM_013121 CD28 antigen Cd28 12.82 BG665360 FMS-like tyrosine kinase 1 Flt1 9.63 NM_012701 Adrenergic receptor, beta 1 Adrb1 8.24 0.46 U20796 Nuclear receptor subfamily 1, group D, member 2 Nr1d2 7.22 NM_017116 Calpain 2 Capn2 6.41 BE097282 Guanine nucleotide binding protein, alpha 12 Gna12 6.21 NM_053328 Basic helix-loop-helix domain containing, class B2 Bhlhb2 5.79 NM_053831 Guanylate cyclase 2f Gucy2f 5.71 AW251703 Tumor necrosis factor receptor superfamily, member 12a Tnfrsf12a 5.57 NM_021691 Twist homolog 2 (Drosophila) Twist2 5.42 NM_133550 Fc receptor, IgE, low affinity II, alpha polypeptide Fcer2a 4.93 NM_031120 Signal sequence receptor, gamma Ssr3 4.84 NM_053544 Secreted frizzled-related protein 4 Sfrp4 4.73 NM_053910 Pleckstrin homology, Sec7 and coiled/coil domains 1 Pscd1 4.69 BE113233 Suppressor of cytokine signaling 2 Socs2 4.68 NM_053949 Potassium voltage-gated channel, subfamily H (eag- Kcnh2 4.60 related), member 2 NM_017305 Glutamate cysteine ligase, modifier subunit Gclm 4.59 NM_017309 Protein phospatase 3, regulatory subunit B, alpha Ppp3r1 4.54 isoform,type 1 NM_012765 5-hydroxytryptamine (serotonin) receptor 2C Htr2c 4.46 NM_017218 V-erb-b2 erythroblastic leukemia viral oncogene homolog Erbb3 4.42 3 (avian) AW918369 Zinc finger protein 191 Zfp191 4.38 NM_031034 Guanine nucleotide binding protein, alpha 12 Gna12 4.38 NM_017020 Interleukin 6 receptor Il6r 4.37 AJ002942
    [Show full text]
  • The TRPM7 Ion Channel Functions in Cholinergic Synaptic Vesicles and Affects Transmitter Release
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Neuron 52, 485–496, November 9, 2006 ª2006 Elsevier Inc. DOI 10.1016/j.neuron.2006.09.033 The TRPM7 Ion Channel Functions in Cholinergic Synaptic Vesicles and Affects Transmitter Release Grigory Krapivinsky,1 Sumiko Mochida,3 (TRPML channels) are presumed intracellular vesicular Luba Krapivinsky,1 Susan M. Cibulsky,1 channels (Di Palma et al., 2002; LaPlante et al., 2002), and David E. Clapham1,2,* but their function in vesicles is not well understood. 1 Howard Hughes Medical Institute Neurotransmitter vesicles release their cargoes by Cardiology fusion with the plasma membrane followed by diffusion Children’s Hospital Boston of their contents into the intercellular space. The fusion 1309 Enders Building process itself is not completely understood, but involves 320 Longwood Avenue a complex of proteins with specialized functions that al- 2 Department of Neurobiology low them to achieve close approximation of the vesicle Harvard Medical School to the plasma membrane and sense changes in [Ca2+] Boston, Massachusetts 02115 that trigger rapid fusion (Sudhof, 2004). Although neuro- 3 Department of Physiology transmitter release requires ion channels, ion channels Tokyo Medical University are best known for their function as the plasma mem- Tokyo 160-8402 brane mediators of the timing and entry of Ca2+ into Japan the cell, which in turn triggers vesicle fusion. Functional ion channels have been recorded in preparations of syn- aptic vesicles (Yakir and Rahamimoff, 1995; Kelly and Summary Woodbury, 1996), and a few well-established plasma membrane channels have been proposed to localize to A longstanding hypothesis is that ion channels are vesicles and regulate their ionic equilibrium (Ehrenstein present in the membranes of synaptic vesicles and et al., 1991; Grahammer et al., 2001), but their molecular might affect neurotransmitter release.
    [Show full text]
  • Study of Selectivity and Permeation in Voltage-Gated Ion Channels
    Study of Selectivity and Permeation in Voltage-Gated Ion Channels By Janhavi Giri, Ph.D. Visiting Research Faculty Division of Molecular Biophysics and Physiology Rush University Medical Center Chicago, IL, USA Email: [email protected] i TABLE OF CONTENTS Page TABLE OF CONTENTS ..................................................................................................... i LIST OF TABLES ............................................................................................................. iii LIST OF FIGURES ........................................................................................................... iv SUMMARY ............................................................................................................... xvi CHAPTER 1. INTRODUCTION ....................................................................................... 1 1.1. Background ................................................................................................... 1 1.2. Overview .................................................................................................... 10 CHAPTER 2. SELF-ORGANIZED MODELS OF SELECTIVITY IN CALCIUM CHANNELS ........................................................................................... 13 2.1. Introduction ................................................................................................ 13 2.2. Methods ...................................................................................................... 19 2.2.1. Model of Channel and Electrolyte ........................................................19
    [Show full text]