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