TABLE 9

CaV3.1 channels

Channel name Cav3.1
Description Voltage-gated calcium channel α1 subunit
Other names T-type, α13.1, α1G
Molecular information Human: 2377aa, O43497, NM_018896, chr. 17q22, CACNA1G1
Rat: 2254aa, O54898, AF027984
Mouse: 2288aa, CAI25956, NM_009783 (see “Comments”)
Associated subunits No biochemical evidence, small changes induced by α2δ12 and α2δ23,4
Functional assays Voltage-clamp, calcium imaging
Current ICa,T
Conductance 7.5pS1
Ion selectivity Sr2+ > Ba2+ = Ca2+
Activation Va = —46 mV, τa = 1 ms at —10 mV5,6
Inactivation Vh = —73 mV, τh = 11 ms at —10 mV5,6
Activators Not established
Gating modifiers Kurtoxin, IC50 = 15 nM7
Blockers No subtype-specific blocker8; selective for Cav3.x relative to Cav1.x and Cav2.x: mibefradil,9,10 U92032,11 penfluridol and pimozide12; nonselective: nickel (IC50 = 250 μM),13 amiloride14
Radioligands None
Channel distribution Brain, especially soma and dendrites of neurons in olfactory bulb, amygdala, cerebral cortex, hippocampus, thalamus, hypothalamus, cerebellum, brain stem (human RNA blots,1,5 rat in situ hybridization15 and immunocytochemistry16); ovary, placenta, heart (especially sinoatrial node; mouse in situ hybridization17)
Physiological functions Thalamic oscillations18
Mutations and pathophysiology Not established
Pharmacological significance May mediate effect of absence antiepileptic drugs such as ethosuximide19 and other thalamocortical dysrhythmias20
Comments Splice variants that differ in their voltage dependence have been cloned5

  • aa, amino acids; chr., chromosome; U92032, 7-[[4-bis(fluorophenyl)methyl]-1-piperazinyl]methyl-2-[(2-hydroxyethyl)a mino]4-(1-methylethyl)-2,4,6-cycloheptatrien-1-one.

  • ↵1. Perez-Reyes E, Cribbs LL, Daud A, Lacerda AE, Barclay J, Williamson MP, Fox M, Rees M, and Lee J-H (1998) Molecular characterization of a neuronal low voltage-activated T-type calcium channel. Nature (Lond) 391:896-900

  • ↵2. Dolphin AC, Wyatt CN, Richards J, Beattie RE, Craig P, Lee J-H, Cribbs LL, Volsen SG, and Perez-Reyes E (1999) The effect of α2δ and other accessory subunits on expression and properties of the calcium channel α1G. J Physiol (Lond) 519.1:35-45

  • ↵3. Gao B, Sekido Y, Maximov A, Saad M, Forgacs E, Latif F, Lerman M, Lee J-H, Perez-Reyes E, Bezprozvanny I, et al. (2000) Functional properties of a new voltage-dependent calcium channel α2δ auxiliary subunit gene (CACNA2D2). J Biol Chem 275:12237-12242

  • ↵4. Hobom M, Dai S, Marais E, Lacinova L, Hofmann F and Klugbauer N (2000) Neuronal distribution and functional characterization of the calcium channel α2δ2 subunit. Eur J Neurosci 12:1217-1226

  • ↵5. Monteil A, Chemin J, Bourinet E, Mennessier G, Lory P, and Nargeot J (2000) Molecular and functional properties of the human α1G subunit that forms T-type calcium channels. J Biol Chem 275:6090-6100

  • ↵6. Klöckner U, Lee JH, Cribbs LL, Daud A, Hescheler J, Pereverzev A, Perez-Reyes E, and Schneider T (1999) Comparison of the Ca2+ currents induced by expression of three cloned α1 subunits, α1G, α1H and α1I, of low-voltage-activated T-type Ca2+ channels. Eur J Neurosci 11:4171-4178

  • ↵7. Chuang RS, Jaffe H, Cribbs L, Perez-Reyes E, and Swartz KJ (1998) Inhibition of T-type voltage-gated calcium channels by a new scorpion toxin. Nat Neurosci 1:668-674

  • ↵8. Heady TN, Gomora JC, Macdonald TL, and Perez-Reyes E (2001) Molecular pharmacology of T-type Ca2+ channels. Jpn J Pharmacol 85:339-350

  • ↵9. Perchenet L, Bénardeau A, and Ertel EA (2000) Pharmacological properties of Cav3.2, a low voltage-activated Ca2 + channel cloned from human heart. Naunyn Schmiedeberg's Arch Pharmacol 361:590-599

  • ↵10. Martin RL, Lee JH, Cribbs LL, Perez-Reyes E, and Hanck DA (2000) Mibefradil block of cloned T-type calcium channels. J Pharmacol Exp Ther 295:302-308

  • ↵11. Avery RB and Johnston D (1997) Ca2+ channel antagonist U-92032 inhibits both T-type Ca2+ channels and Na+ channels in hippocampal CA1 pyramidal neurons. J Neurophysiol 77:1023-1028

  • ↵12. Santi CM, Cayabyab FS, Sutton KG, McRory JE, Mezeyova J, Hamming KS, Parker D, Stea A, and Snutch TP (2002) Differential inhibition of T-type calcium channels by neuroleptics. J Neurosci 22:396-403

  • ↵13. Lee JH, Gomora JC, Cribbs LL, and Perez-Reyes E (1999) Nickel block of three cloned T-type calcium channels: low concentrations selectively block α1H. Biophys J 77:3034-3042

  • ↵14. Lacinova L, Klugbauer N, and Hofmann F (2000) Regulation of the calcium channel α1G subunit by divalent cations and organic blockers. Neuropharmacology 39:1254-1266

  • ↵15. Talley EM, Cribbs LL, Lee JH, Daud A, Perez-Reyes E, and Bayliss DA (1999) Differential distribution of three members of a gene family encoding low voltage-activated (T-type) calcium channels. J Neurosci 19:1895-1911

  • ↵16. Craig PJ, Beattie RE, Folly EA, Banerjee MD, Reeves MB, Priestley JV, Carney SL, Sher E, Perez-Reyes E, and Volsen SG (1999) Distribution of the voltage-dependent calcium channel α1G subunit mRNA and protein throughout the mature rat brain. Eur J Neurosci 11:2949-2964

  • ↵17. Bohn G, Moosmang S, Conrad H, Ludwig A, Hofmann F, and Klugbauer N (2000) Expression of T- and L-type calcium channel mRNA in murine sinoatrial node. FEBS Lett 481:73-76

  • ↵18. Perez-Reyes E (2003) Molecular physiology of low-voltage-activated T-type calcium channels. Physiol Rev 83:117-161

  • ↵19. Gomora JC, Daud AN, Weiergräber M, and Perez-Reyes E (2001) Block of cloned human T-type calcium channels by succinimide antiepileptic drugs. Mol Pharmacol 60:1121-1132

  • ↵20. Llinás RR, Ribary U, Jeanmonod D, Kronberg E, and Mitra PP (1999) Thalamocortical dysrhythmia: a neurological and neuropsychiatric syndrome characterized by magnetoencephalography. Proc Natl Acad Sci USA 96:15222-15227