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| RESEARCH INTERESTS My laboratory works on structure, function and modulation of neuronal voltage-gated calcium channels. Using a combination molecular biological, electrophysiological and biochemical techniques, we are investigating the molecular determinants which govern the interactions of presynaptic calcium channels with G proteins and proteins of the vesicle release complex (SNAREs). A second major research direction of the laboratory is the elucidation of the structural determinants which underlie calcium channel function, with a particular focus on voltage dependent inactivation. Through a collaboration with NeuroMed Technologies. Inc. we participate in the development of novel calcium channel antagonists. PUBLICATIONS Asfaha S, Cenac N, Houle S, Altier C, Papez MD, Nguyen C, Steinhoff M, Chapmat K, Zamponi GW, Vergnolle N. Protease-activated receptor-4: a novel mechanism of inflammatory pain modulation. Br J Pharmacol 150:176-185, 2007. Grant AD, Cottrell GS, Amadesi S, Trevisani M, Niocoletti P, Materazzi S, Altier C, Cenac N, Zamponi GW, Bautista-Cruz F, Lopez CB, Joseph EK, Levine JD, Liedtke W, Vanner S, Vergnolle S, Geppetti P, Bunnett NW. Protease-activated receptor 2 sensitizes the transient receptor potential vanilloid 4 ion channel to cause mechanical hyperalgesia in mice. J Physiol 578:715-733, 2007. McKay BE, McRory JE, Molineux ML, Hamid J, Snutch TP, Zamponi GW, Turner RW. Ca(V)3 T-type calcium channel isoforms differentially distribute to somatic and dendritic compartments in rat central neurons. Eur J Neurosci 24:2581-2594, 2006. Schroeder CI, Doering CJ, Zamponi GW, Lewis RJ. N-type calcium channel blockers: novel therapeutics for the treatment of pain. Med Chem 2:535-543, 2006. Tedford HW, Zamponi GW. Direct G protein modulation of Cav2 calcium channels. Pharmacol Rev 58:837-862, 2006. Altier C, Zamponi GW. Opioid, cheating on its receptors, exacerbates pain. Nat Neurosci 9:1465-1467, 2006. Hamid J, Peloquin JB, Monteil A, Zamponi GW. Determinants of the differential gating properties of Cav3.1 and Cav3.3T-type channels: a role of domain IV? Neuroscience 143:717-728, 2006. Evans RM, Zamponi GW. Presynaptic Ca2+ channels-integration centers for neuronal signaling pathways. Trends Neurosci 29:617-624, 2006. Iftinca M, McKay BE, Snutch TP, McRory JE, Turner RW, Zamponi GW. Temperature dependence of T-type calcium channel gating. Neuroscience 142:1031-1042, 2006. Szabo Z, Obermair GJ, Cooper CB, Zamponi GW, Flucher BE. Role of the synprint site in presynaptic targeting of the calcium channel CaV2.2 in hippocampal neurons. Eur J Neurosci 24:709-718, 2006. Policha A, Daneshtalab N, Chen L, Dale LB, Altier C, Khosravani H, Thomas WG, Zamponi GW, Ferguson SS. Role of angiotensin II type 1A receptor phosphorylation, phospholipase D, and extracellular calcium in isoform-specific protein kinase C membrane translocation responses. J Biol Chem 281:26340-26349, 2006. Mcleod GT, Chen L, Karunanithi S, Peloquin JB, Atwood HL, McRory JE, Zamponi GW, Charlton MP. The Drosophila cacts2 mutation reduces presynaptic Ca2+ entry and defines an important element in Cav2.1 channel inactivation. Eur J Neurosci 23:3230-3244, 2006. Khosravani H, Zamponi GW. Voltage-gated calcium channels and idiopathic generalized epilepsies. Physiol Rev 86:941-966, 2006. Schenning M, Proctor DT, Ragnarsson L, Barbier J, Lavidis NA, Molgo JJ, Zamponi GW, Schiavo G, Meunier FA. Glycerotoxin stimulates neurotransmitter release from N-type Ca2+ channel expressing neurons. J Neurochem 98:894-904, 2006. Tedford HW, Kisilevsky AE, Peloquin JB, Zamponi GW. Scanning mutagenesis reveals a role for serine 189 of the heterotrimeric G-protein beta 1 subunit in the inhibition of N-type calcium channels. J Neurophysiol 96:465-470, 2006. Molineux ML, McRory JE, McKay BE, Hamid J, Mehaffey WH, Rehak R, Snutch TP, Zamponi GW, Turner RW. Specific T-type calcium channel isoforms are associated with distinct burst phenotypes in deep cerebellar nuclear neurons. Proc Natl cad Sci USA 103:5555-5560, 2006. Gui P, Su X, Ling S, Stotz SC, Winkfein RJ, Wilson E, Davis GE, Braun AP, Zamponi GW, Davis MJ. Integrin receptor activation triggers converging regulation of Cav1.2 calcium channels by c-Src and protein kinase A pathways. J Biol Chem 281:4015-4025, 2006. Peloquin JB, Khosravani H, Barr W, Bladen C, Evans R, Mazeyova J, Parker D, Snutch TP, McRory JE, Zamponi GW. Functional analysis of Ca3.2 T-type calcium channel mutations linked to childhood absence epilepsy. Epilepsia 47:655-658, 2006. Hall DD, Feekes JA, Arachchige DAS, Shi M, Hamid J, Chen L, Strack S, Zamponi GW, Home MC, Hell JW. Binding of protein phosphatase 2A to the L-type calcium channel Cav1.2 next to Ser1928, its main PKA site, is critical for Ser1928 dephosphorylation. Biochemistry 45:3448-3459, 2006. Micu I, Jiang Q, Coderre E, Ridsdale A, Zhang L, Woulfe J, Yin X, Trapp BD, McRory JE, Rehak R, Zamponi GW, Wang W, Stys PK. NMDA receptors mediate calcium accumulation in myelin during chemical ischaemia. Nature 439:988-992, 2006. Altier C, Khosravani H, Evans RM, Hameed S, Peloquin JB, Vartian BA, Chen L, Beedle AM, Ferguson SS, Mezghrani A, Dubel SJ, Bourinet E, McRory JE, Zamponi GW. ORL1 receptor-mediated internalization of N-type calcium channels. Nat Neurosci 9:31-40, 2006. Spafford JD, Dunn T, Smit AB, Syed NI and Zamponi GW. J Neurophysiol 95:42-52, 2006. Khosravani H, Altier C, Zamponi GW and Colicos MA. The Arg473Cys-neuroligin-1 mutation modulates NMDA mediated synaptic transmission and receptor distribution in hippocampal neurons. FEBS Letters 579:6587-6594, 2005. Swayne LA, Hameed S, Chen L, Barr W, Charlesworth E, Colicos MA, Zamponi GW and Braun JEA. Huntingtin disrupts syntaxin modulation of N-type calcium channels. Molecular and Cellular Neuroscience 30:339-351, 2005. Doering CJ, Hamid J, Simms BA, McRory JE, and Zamponi GW. Cav1.4 encodes a calcium channel with low open probability and unitary conductance. Biophys J 89:3042-3048, 2005. Bourinet E and Zamponi GW. Voltage gated calcium channels as targets for analgesics. Current Topics in Medicinal Chemistry 5:539-547, 2005. Khosravani H, Bladen C, Parker D, Snutch TP, McRory JE and Zamponi GW. Effects of Cav3.2 channel mutations linked to idiopathic generalized epilepsy. Annals of Neurology 57:745-749, 2005. Kuzmiski JB, Barr W, Zamponi GW and MacVicar BA. Topiramate inhibits the initiation of plateau potentials in CA1 neurons by depressing R-type calcium channels. Epilepsia 46:481-489, 2005. Ouardouz M, Zamponi GW, Barr W, Kiedrowski L and Stys PK. Protection of ischemic rat spinal white matter: dual action of KB-R7943 on Na+/Ca2+ exchange and L-type Ca2+ channels. Neuropharmacology 48:556-575, 2005. Jarvis SE and Zamponi GW. Masters of slaves? Vesicle release machinery and the regulation of presynaptic calcium channels. Cell Calcium 37:483-488, 2005. French RJ and Zamponi GW. Voltage-gated sodium and calcium channels in nerve, muscle and heart. IEEE Transaction in Nanobioscience 4:58-69, 2005. Doering CJ and Zamponi GW. Molecular pharmacology of non-L-type calcium channels. Current Pharmaceutical Design 11:1887-1898, 2005. Nirdosh A and Zamponi GW. Determinants of G protein inhibition of presynaptic calcium channels. Determinants of G protein inhibition of resynaptic calcium channels. Eurekah Bioscience 1:285-291, 2005. Tedford HW, Gilles N, Menez A, Doering CJ, Zamponi GW and King GF. Scanning mutagenesis of omega-atracotoxin-Hv1a reveals a spatially restricted epitope that confers selective activity against invertebrate calcium channels. J Biol Chem 279:44133-44140, 2004. Altier C and Zamponi GW. Targeting calcium channels to treat pain: T-type versus N-type. Trends in Pharmacological Sciences 25:465-470, 2004. Spafford JD, van Minnen J, Larsen P, Smit AB, Syed NI and Zamponi GW. Uncoupling of calcium channel alpha1 and beta subunits in developing neurons. J Biol Chem 279:41157-41167, 2004. Doering CJ, Kisilevsky AE, Feng ZP, Arnot MI, Peloquin J, Nirdosh A, Hamid J, Barr W, Simms BA, Winkfein FJ and Zamponi GW. A single Gbeta subunit locus controls crosstalk between PKC and G protein regulation of N-type calcium channels. J Biol Chem 279:27909-27917, 2004. Mould J, Yasuda T, Schoreder CI, Beedle AM, Coering CJ, Zamponi GW, Adams DJ and Lewis RJ. The alpha2delta auxiliary subunit reduces affinity of omega-conotoxins for recombinant N-type calcium channels. J Biol Chem 279:34705-34714, 2004. Yasuda T, Chen L, Barr W, McRory JE, Lewis RJ, Adams DJ and Zamponi GW. Auxiliary subunit regulation of high- voltage activated calcium channels expressed in mammalian cells. Eur J Neurosci 20:1-13, 2004. Latour I, Louw DF, Beedle AM, Hamid J, Sutherland GR and Zamponi GW. Expression of T-type calcium channel splice variants in human glioma. Glia 48:112-119, 2004. Khosravani H, Altier C, Simms B, Hamming K, Snutch TP, Mezeyova J, McRory JE and Zamponi GW. Gating effects of mutations I the Cav3.2 T-type calcium channel associated with Childhood Absence Epilepsy. J Biol Chem 279:9681-9684, 2004. Zamponi GW and McCleskey EW. Splicing it up: a variant of the N-type calcium channel specific for pain. Neuron 41:3-4, 2004. Beedle AM, McRory JE, Doering CJ, Altier C, Poirot P, Barrere C, Hamid J, Nargeot J, Bpiromet E and Zamponi GW. Agonist independent modulation of N-type calcium channels by ORL1 receptors – evidence for a channel-receptor signaling complex. Nature Neuroscience 7:118-125, 2004. McRory JE, Hamid J, Doering CJ, Garcia E, Parker R, Hamming K, Chen L, Hildebrand M, Beedle AM, Feldcamp L, Zamponi GW and Snutch TP. The CACNA1F gene implicated in congenital night blindness encodes an L-type calcium channel with unique biophysical properties and tissue distribution. J Neurosci 24:1707-1718, 2004. Stotz SC, Barr W, McRory JE, Chen L, Jarvis JE and Zamponi GW. Several structural domains contribute to the regulation of N-type calcium channel inactivation by the beta 3 subunit J Biol Chem 279:3793-3800, 2004. Stotz SC, Jarvis SE and Zamponi GW. Functional roles of cytoplastmic loops and pore lining transmembrane helices in the voltage-dependent inactivation of HVA calcium channels. J Physiol 554:263-273, 2004. Ouardouz, M., Nikolaeva, M., Coderre, E., Zamponi, G.W., McRory, J.E., Trapp, B., Yin, X., Wang, W., Woulfe, J., and Stys, P.K. Depolarization-induced Ca2+ release in ischemic spinal cord white matter involves L-type Ca2+ channel activation of ryanodine receptors. Neuron. 40: 53-63, 2003. Zamponi, G.W. Calmodulin lobotomized: novel insights into calcium regulation of voltage gated calcium channels. Neuron. 39: 879-881, 2003. Zamponi, G.W. The L-type calcium channel C-terminus: Sparking interest beyond its role in calcium-dependent inactivation. J. Physiol. 552: 333, 2003. Szule, J.A., Jarvis, S.E., Hibbert, J.E., Spafford, J.D., Braun, J.E.A., Zamponi. G.W., Wessel, G., and Coorssen, J.R. Specific presynaptic proteins function upstream of membrane triggered fusion. J. Biol. Chem. 278: 24251-24254, 2003. Zamponi, G.W. Regulation of presynaptic calcium channels by synaptic proteins. J. Pharmacol. Sci. 92: 79-83, 2003. Bertram, R., Swanson, J., Yousef, M., Feng, Z.P., and Zamponi, G.W. A minimal model for G protein-mediated synaptic facilitation and depression. J. Neurophysiol. 90: 1643-1653, 2003. Spafford, J.D., Chen, L., Feng, Z.P., Smit, A.B., and Zamponi, G.W. Expression and modulation of an invertebrate presynaptic calcium channel alpha 1 subunit homolog. J. Biol. Chem. 278: 21178 - 21187, 2003. Feng, Z.P., Doering, C.J., Winkfein, R.J., Beedle, A.M., Spafford, J.D., and Zamponi, G.W. Determinants of inhibition of transiently expressed calcium channels by omega-conotoxin GVIA and MVIIA. J. Biol. Chem. 278: 20171-20178, 2003. Spafford, J.D., and Zamponi, G.W. Functional interactions between presynaptic calcium channels and the neurotransmitter release machinery. Curr. Op. Neurobiol. 13: 308-314, 2003. Miller, L.C., Swayne, L.A., Kay, J.G., Feng, Z.P., Jarvis, S.E., Zamponi. G.W., and Braun, J.E.A. Distinct modes of action by the J domain and cysteine string domain of CSP modulate G protein inhibition of N -type calcium channels. J. Cell. Sci. 116: 2967- 2974, 2003. Spafford, J.D., Munno, D.W., van Nierop, P., Jarvis, S.E., Feng, Z.P., Gallin, G.W., Smit, A.B., Zamponi, G.W.*, and Syed, N.I. Calcium channel structural determinants of synaptic transmission between identified invertebrate neurons. J. Biol. Chem. 278: 4258-4267, 2003. (* corresponding author) Zamponi, G.W., Stotz, S.C., Staples, R.J., Rogers, T.A., and Natale, N.R. Unique structure activity relationship for -isoxazolyl-1,4-dihydropyridines. J. Med. Chem. 46: 87-96, 2003. Latour, I., Hamid, J., Beedle, A.M., Zamponi, G.W., and MacVicar, BA. 2003. Expression of voltage gated Ca2+ channel subtypes in cultured astrocytes. Glia. 41: 347-353, 2003. Doering, C.J., and Zamponi, G.W. 2003. Molecular pharmacology of high voltage activated calcium channels. J. Bioenerg. Biomem. 35:491-505, 2003. Jarvis, S.E., and Zamponi, G.W. 2001.Interactions between presynaptic calcium channels, cytoplasmic messengers, and proteins of the synaptic vesicle release complex. Trends Pharmacol. Sci. 22:519-525, 2001. Stotz, S.C., and Zamponi, G.W. 2001. Identification of inactivation determinants in the domain IIS6 region of high-voltage activated calcium channels. J. Biol. Chem. 276:33001-33010, 2001. Bourinet, E., Stotz, S.C., Spaetgens, R.L., Dayanithi, G., Lemos, J., Nargeot, J., and Zamponi, G.W. 2001. Interaction of SNX482 with domains III and IV inhibits activation gating of alpha 1E calcium channels. Biophys J. 81: 79-88. Lu, Q., AtKisson, M.S., Jarvis, S.E., Feng, Z.-P., Zamponi, G.W., and Dunlap, K.D. 2001. Syntaxin 1A supports voltage-dependent inhibition of alpha 1B Ca2+ channels by Gbetagamma in chick sensory neurons. J. Neurosci. 21: 2949-2957. Jarvis, S.E., and Zamponi, G.W. 2001. Distinct molecular determinants govern syntaxin 1A mediated inactivation and G protein inhibition of N-type calcium channels. J. Neurosci. 21: 2939-2948. Feng, Z.-P., Hamid, J., Doering, C., Bosey, G.M., Snutch, T.P., and Zamponi, G.W. 2001. Residue G1326 of the N-type calcium channel alpha 1 subunit controls reversibility of w-conotoxin GVIA and MVIIA block. J. Biol. Chem. 276: 15728-15735. Altier, C., Spaetgens, R.L., Nargeot, J., Bourinet, E., and Zamponi, G.W. 2001. Multiple structural elements contribute to voltage-dependent facilitation of neuronal alpha 1C L-type calcium channels. Neuropharmacology. 40:1050-1057. Feng, Z.-P., Hamid, J., Doering, C., Jarvis, S.E., Bosey, G.M., Bourinet, E., Snutch, T.P., and Zamponi, G.W. 2001. Amino acid residues outside of the pore region contribute to N-type calcium channel permeation. J. Biol. Chem. 276: 5726-5730. Zamponi, G.W. 2001. Determinants of G protein inhibition of presynaptic calcium channels. Cell Biochemistry and Biophysics. 34: 79-94. Stotz, S.C., and Zamponi, G.W. 2001. Structural determinants of fast inactivation of high voltage activated calcium channels. Trends Neurosci. 24: 176-182. Snutch, T.P., Sutton, K.G., and Zamponi, G.W. 2001. Voltage-dependent calcium channels - beyond dihydropyridine antagonists. Curr. Opin. Pharmacol. 1: 11-16. Book
Chapters/Contributions Voltage-dependent inactivation of voltage gated calcium channels. Voltage Gated Calcium Channels, Kluwer/Landes Bioscience, 2004 Determinants of G protein inhibition of presynaptic calcium channels. Voltage Gated Calcium Channels, Kluwer/Landes Bioscience, 2004. Books
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