Voltage-gated calcium channels
More information on this family may be found on the IUPHAR-DB family and introduction pages.
Calcium (Ca2+) channels are voltage-gated ion channels present in the membrane of most excitable cells. The nomenclature for Ca2+channels was proposed by [2] and approved by the NC-IUPHAR subcommittee on Ca2+ channels [1]. Ca2+ channels form hetero-oligomeric complexes. The α1 subunit is pore-forming and provides the extracellular binding site(s) for practically all agonists and antagonists. The 10 cloned α-subunits can be grouped into three families: (1) the high-voltage activated dihydropyridine-sensitive (L-type, CaV1.x) channels; (2) the high-voltage activated dihydropyridine-insensitive (CaV2.x) channels and (3) the low-voltage-activated (T-type, CaV3.x) channels. Each α1 subunit has four homologous repeats (I–IV), each repeat having six transmembrane domains and a pore-forming region between transmembrane domains S5 and S6. Gating is thought to be associated with the membrane-spanning S4 segment, which contains highly conserved positive charges. Many of the α1-subunit genes give rise to alternatively spliced products. At least for high-voltage activated channels, it is likely that native channels comprise co-assemblies of α1, β and α2–δ subunits. The γ subunits have not been proven to associate with channels other than α1s. The α2–δ1 and α2–δ2 subunits bind gabapentin and pregabalin.
Unless otherwise stated all data refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).
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Bauer, CS; Tran-Van-Minh, A; Kadurin, I; Dolphin, AC. (2010) A new look at calcium channel α2δ subunits. Curr. Opin. Neurobiol., 20 (5): 563-71. [PMID:20579869]
Belardetti, F; Zamponi, GW. (2008) Linking calcium-channel isoforms to potential therapies. Curr Opin Investig Drugs, 9 (7): 707-15. [PMID:18600576]
Buraei, Z; Yang, J. (2010) The ß subunit of voltage-gated Ca2+ channels. Physiol. Rev., 90 (4): 1461-506. [PMID:20959621]
Catterall, WA. (2000) Structure and regulation of voltage-gated Ca2+ channels. Annu. Rev. Cell Dev. Biol., 16: 521-55. [PMID:11031246]
Catterall, WA. (2011) Voltage-gated calcium channels. Cold Spring Harb Perspect Biol, 3 (8): a003947. [PMID:21746798]
Catterall, WA; Dib-Hajj, S; Meisler, MH; Pietrobon, D. (2008) Inherited neuronal ion channelopathies: new windows on complex neurological diseases. J. Neurosci., 28 (46): 11768-77. [PMID:19005038]
Catterall, WA; Perez-Reyes, E; Snutch, TP; Striessnig, J. (2005) International Union of Pharmacology. XLVIII. Nomenclature and structure-function relationships of voltage-gated calcium channels. Pharmacol. Rev., 57 (4): 411-25. [PMID:16382099]
Davies, A; Hendrich, J; Van Minh, AT; Wratten, J; Douglas, L; Dolphin, AC. (2007) Functional biology of the alpha(2)delta subunits of voltage-gated calcium channels. Trends Pharmacol. Sci., 28 (5): 220-8. [PMID:17403543]
Dolphin, AC. (2003) G protein modulation of voltage-gated calcium channels. Pharmacol. Rev., 55 (4): 607-27. [PMID:14657419]
Dolphin, AC. (2009) Calcium channel diversity: multiple roles of calcium channel subunits. Curr. Opin. Neurobiol., 19 (3): 237-44. [PMID:19559597]
Elmslie, KS. (2004) Calcium channel blockers in the treatment of disease. J. Neurosci. Res., 75 (6): 733-41. [PMID:14994334]
Ertel, EA; Campbell, KP; Harpold, MM; Hofmann, F; Mori, Y; Perez-Reyes, E; Schwartz, A; Snutch, TP; Tanabe, T; Birnbaumer, L; Tsien, RW; Catterall, WA. (2000) Nomenclature of voltage-gated calcium channels. Neuron, 25 (3): 533-5. [PMID:10774722]
Gao, L. (2010) An update on peptide drugs for voltage-gated calcium channels. Recent Pat CNS Drug Discov, 5 (1): 14-22. [PMID:19751208]
Han, TS; Teichert, RW; Olivera, BM; Bulaj, G. (2008) Conus venoms - a rich source of peptide-based therapeutics. Curr. Pharm. Des., 14 (24): 2462-79. [PMID:18781995]
Hofmann, F; Lacinová, L; Klugbauer, N. (1999) Voltage-dependent calcium channels: from structure to function. Rev. Physiol. Biochem. Pharmacol., 139: 33-87. [PMID:10453692]
Kochegarov, AA. (2003) Pharmacological modulators of voltage-gated calcium channels and their therapeutical application. Cell Calcium, 33 (3): 145-62. [PMID:12600802]
Lewis, RJ; Garcia, ML. (2003) Therapeutic potential of venom peptides. Nat Rev Drug Discov, 2 (10): 790-802. [PMID:14526382]
Lory, P; Chemin, J. (2007) Towards the discovery of novel T-type calcium channel blockers. Expert Opin. Ther. Targets, 11 (5): 717-22. [PMID:17465728]
Nelson, MT; Todorovic, SM; Perez-Reyes, E. (2006) The role of T-type calcium channels in epilepsy and pain. Curr. Pharm. Des., 12 (18): 2189-97. [PMID:16787249]
Perez-Reyes, E. (2003) Molecular physiology of low-voltage-activated t-type calcium channels. Physiol. Rev., 83 (1): 117-61. [PMID:12506128]
Pexton, T; Moeller-Bertram, T; Schilling, JM; Wallace, MS. (2011) Targeting voltage-gated calcium channels for the treatment of neuropathic pain: a review of drug development. Expert Opin Investig Drugs, 20 (9): 1277-84. [PMID:21740292]
Taylor, CP; Angelotti, T; Fauman, E. (2007) Pharmacology and mechanism of action of pregabalin: the calcium channel alpha2-delta (alpha2-delta) subunit as a target for antiepileptic drug discovery. Epilepsy Res., 73 (2): 137-50. [PMID:17126531]
Terlau, H; Olivera, BM. (2004) Conus venoms: a rich source of novel ion channel-targeted peptides. Physiol. Rev., 84 (1): 41-68. [PMID:14715910]
Triggle, DJ. (2006) L-type calcium channels. Curr. Pharm. Des., 12 (4): 443-57. [PMID:16472138]
Triggle, DJ. (2007) Calcium channel antagonists: clinical uses--past, present and future. Biochem. Pharmacol., 74 (1): 1-9. [PMID:17276408]
Trimmer, JS; Rhodes, KJ. (2004) Localization of voltage-gated ion channels in mammalian brain. Annu. Rev. Physiol., 66: 477-519. [PMID:14977411]
Williams, JA; Day, M; Heavner, JE. (2008) Ziconotide: an update and review. Expert Opin Pharmacother, 9 (9): 1575-83. [PMID:18518786]
Yamamoto, T; Takahara, A. (2009) Recent updates of N-type calcium channel blockers with therapeutic potential for neuropathic pain and stroke. Curr Top Med Chem, 9 (4): 377-95. [PMID:19442208]
Yu, FH; Catterall, WA. (2004) The VGL-chanome: a protein superfamily specialized for electrical signaling and ionic homeostasis. Sci. STKE, 2004 (253): re15. [PMID:15467096]
Zamponi, GW; Lewis, RJ; Todorovic, SM; Arneric, SP; Snutch, TP. (2009) Role of voltage-gated calcium channels in ascending pain pathways. Brain Res Rev, 60 (1): 84-9. [PMID:19162069]
1. Catterall, WA; Perez-Reyes, E; Snutch, TP; Striessnig, J. (2005) International Union of Pharmacology. XLVIII. Nomenclature and structure-function relationships of voltage-gated calcium channels. Pharmacol. Rev., 57 (4): 411-25. [PMID:16382099]
2. Ertel, EA; Campbell, KP; Harpold, MM; Hofmann, F; Mori, Y; Perez-Reyes, E; Schwartz, A; Snutch, TP; Tanabe, T; Birnbaumer, L; Tsien, RW; Catterall, WA. (2000) Nomenclature of voltage-gated calcium channels. Neuron, 25 (3): 533-5. [PMID:10774722]
3. Williams, JA; Day, M; Heavner, JE. (2008) Ziconotide: an update and review. Expert Opin Pharmacother, 9 (9): 1575-83. [PMID:18518786]
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In many cell types, P and Q current components cannot be adequately separated and many researchers in the field have adopted the terminology ‘P/Q-type’ current when referring to either component. Ziconotide (a synthetic peptide equivalent to ω-conotoxin MVIIA) has been approved for the treatment of chronic pain [3].