TABLE 10

CaV3.2 channels

Channel name Cav3.2
Description Voltage-gated calcium channel α1 subunit
Other names T-type, α13.2, α1H
Molecular information Human: 2353aa, O95180, AF051946, chr0.16p13.3, CACNA1H1
Rat: 2359aa, AAG35187, AF290213
Mouse: 2365aa, NP_067390, NM_021415
Associated subunits Not established
Functional assays Voltage-clamp, calcium imaging
Current ICa,T
Conductance 9pS2
Ion selectivity Ba2+ = Ca2+
Activation Va = –46 mV, τa = 2 ms at –10 mV3
Inactivation Vh = –72 mV, τh = 16 ms at –10 mV3
Activators None
Gating modifiers Kurtoxin4
Blockers Cav3.2 is more sensitive than Cav3.1 to block by nickel (IC50 = 12 μM)5 and possibly phenytoin6 and amiloride2,7; selective for Cav3.x relative to Cav1.x and Cav2.x: mibefradil,8,9 U92032,10 penfluridol and pimozide,11 and amiloride12; nonselective: nimodipine,2 anesthetics5
Radioligands None
Channel distribution Kidney (human Northern1), rat smooth muscle (RT-PCR13), liver (human Northern1), adrenal cortex (rat, bovine; in situ hybridization and RT-PCR14), brain (especially in olfactory bulb, striatum, cerebral cortex, hippocampus, reticular thalamic nucleus; rat in situ hybridization15), and heart (especially sinoatrial node; mouse in situ hybridization16)
Physiological functions Smooth muscle contraction,17 smooth muscle proliferation,18 aldosterone secretion,19 cortisol secretion20
Mutations and pathophysiology Single nucleotide polymorphisms associated with childhood absence epilepsy patients in a Chinese population21
Pharmacological significance May mediate effect of absence antiepileptic drugs such as ethosuximide22 and other thalamocortical dysrhythmias23; potential drug target in hypertension and angina pectoris24
Comments Splice variation found in the linker connecting repeat 3 and 425

  • aa, amino acids; chr., chromosome; RT-PCR, reverse-transcriptase-polymerase chain reaction.

  • ↵1. Cribbs LL, Lee JH, Yang J, Satin J, Zhang Y, Daud A, Barclay J, Williamson MP, Fox M, Rees M, et al. (1998) Cloning and characterization of α1H from human heart, a member of the T-type Ca2+ channel gene family. Circ Res 83:103-109

  • ↵2. Williams ME, Washburn MS, Hans M, Urrutia A, Brust PF, Prodanovich P, Harpold MM, and Stauderman KA (1999) Structure and functional characterization of a novel human low-voltage activated calcium channel. J Neurochem 72:791-799

  • ↵3. 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

  • ↵4. 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

  • ↵5. 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

  • ↵6. Todorovic SM, Perez-Reyes E, and Lingle CJ (2000) Anticonvulsants but not general anesthetics have differential blocking effects on different T-type current variants. Mol Pharmacol 58:98-108

  • ↵7. 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

  • ↵8. 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

  • ↵9. 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

  • ↵10. 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

  • ↵11. 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

  • ↵12. Tang C-M, Presser F, and Morad M (1988) Amiloride selectively blocks the low threshold (T) calcium channel. Science 240:213-215

  • ↵13. Hansen PB, Jensen BL, Andreasen D, and Skøtt O (2001) Differential expression of T- and L-type voltage-dependent calcium channels in renal resistance vessels. Circ Res 89:630-638

  • ↵14. Schrier AD, Wang H, Talley EM, Perez-Reyes E, and Barrett PQ (2001) α1H T-type Ca2+ channel is the predominant subtype expressed in bovine and rat zona glomerulosa. Am J Physiol Cell Physiol 280:C265-C272

  • ↵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. 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

  • ↵17. Sarsero D, Fujiwara T, Molenaar P, and Angus JA (1998) Human vascular to cardiac tissue selectivity of L- and T-type calcium channel antagonists. Br J Pharmacol 125:109-119

  • ↵18. Schmitt R, Clozel JP, Iberg N, and Bühler FR (1995) Mibefradil prevents neointima formation after vascular injury in rats. Possible role of the blockade of the T-type voltage-operated calcium channel. Arterioscler Thromb Vasc Biol 15:1161-1165

  • ↵19. Rossier MF, Ertel EA, Vallotton MB, and Capponi AM (1998) Inhibitory action of mibefradil on calcium signaling and aldosterone synthesis in bovine adrenal glomerulosa cells. J Pharmacol Exp Ther 287:824-831

  • ↵20. Gomora JC, Xu L, Enyeart JA, and Enyeart JJ (2000) Effect of mibefradil on voltage-dependent gating and kinetics of T-type Ca2+ channels in cortisol-secreting cells. J Pharmacol Exp Ther 292:96-103

  • ↵21. Chen YC, Lu JJ, Pan H, Zhang YH, Wu HS, Xu KM, Liu XY, Jiang YW, Bao XH, Yao ZJ, et al. (2003) Association between genetic variation of CACNA1H and childhood absence epilepsy. Ann Neurol 54:239-243

  • ↵22. 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

  • ↵23. Llinás R, 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

  • ↵24. Ertel SI, Ertel EA, and Clozel JP (1997) T-type Ca2+ channels and pharmacological blockade: potential pathophysiological relevance. Cardiovasc Drugs Ther 11:723-739

  • ↵25. Jagannathan S, Punt EL, Gu Y, Arnoult C, Sakkas D, Barratt CLR, and Publicover SJ (2002) Identification and localization of T-type voltage-operated calcium channel subunits in human male germ cells. Expression of multiple isoforms. J Biol Chem 277:8449-8456