CaV3.3 channels

Channel name Cav3.3
Description Voltage-gated calcium channel α1 subunit
Other names T-type, α13.3, α1I
Molecular information Human: 2251aa, AAM67414, AF393329, chr. 22q13.1, CACNA1I1
Rat: 1835aa, AF086827, AAD17796
Mouse 2753aa: XP_139476, XM_139476
Associated subunits No biochemical evidence, small changes induced by γ22
Functional assays Voltage-clamp, calcium imaging
Current ICa,T
Conductance 11pS1
Ion selectivity Ba2+ = Ca2+
Activation Va = –44 mV, τa = 7 ms at –10 mV4
Inactivation Vh = –72 mV, τh = 69 ms at –10 mV4
Activators Not established
Gating modifiers None
Blockers No subtype-specific blocker5; selective for Cav3.x relative to Cav1.x and Cav2.x: mibefradil,6,7 U92032,8 penfluridol,9 pimozide9; nonselective: nickel (IC50 = 216 μM)10
Radioligands None
Channel distribution Brain, especially olfactory bulb, striatum, cerebral cortex, hippocampus, reticular nucleus, lateral habenula, cerebellum (rat in situ hybridization,11 human Northern12
Physiological functions Thalamic oscillations13
Mutations and pathophysiology Not established
Pharmacological significance May mediate effect of absence antiepileptic drugs such as ethosuximide14 and other thalamocortical dysrhythmias15
Comments Splice variants have been reported16
  • aa, amino acids; chr., chromosome.

  • 1. Lee JH, Daud AN, Cribbs LL, Lacerda AE, Pereverzev A, Klöckner U, Schneider T, and Perez-Reyes E (1999) Cloning and expression of a novel member of the low voltage-activated T-type calcium channel family. J Neurosci 19:1912-1921

  • 2. Green PJ, Warre R, Hayes PD, McNaughton NC, Medhurst AD, Pangalos M, Duckworth DM, and Randall AD (2001) Kinetic modification of the α1I subunit-mediated T-type Ca2+ channel by a human neuronal Ca2+ channel γ subunit. J Physiol (Lond) 533:467-478

  • 3. McRory JE, Santi CM, Hamming KS, Mezeyova J, Sutton KG, Baillie DL, Stea A, and Snutch TP (2001) Molecular and functional characterization of a family of rat brain T-type calcium channels. J Biol Chem 276:3999-4011

  • 4. 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

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

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

  • 7. 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

  • 8. 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

  • 9. 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

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

  • 11. 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

  • 12. Monteil A, Chemin J, Leuranguer V, Altier C, Mennessier G, Bourinet E, Lory P, and Nargeot J (2000) Specific properties of T-type calcium channels generated by the human α1I subunit. J Biol Chem 275:16530-16535

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

  • 14. 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

  • 15. 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

  • 16. Mittman S, Guo J, Emerick MC, and Agnew WS (1999) Structure and alternative splicing of the gene encoding α1I, a human brain T calcium channel α1 subunit. Neurosci Lett 269:121-124