Molecular Biology of T-Type Calcium Channels

E.      Perez-Reyes; P.      Lory

Abstract

This review summarizes recent progress on the molecular biology of low voltage-gated, T-type, calcium channels. The genes encoding these channels were identified by molecular cloning of cDNAs that were similar in sequence to the α1 subunit of high voltage-activated Ca2+ channels. Three T-channel genes were identified: CACNA1G, encoding Cav3.1; CACNA1H, encoding Cav3.2; and CACNA1I, encoding Cav3.3. Recent studies have focused on how these genes give rise to alternatively spliced transcripts, and how this splicing affects channel activity. A second area of focus is on how single nucleotide polymorphisms (SNPs) alter channel activity. Based on their distribution in thalamic nuclei, coupled with the physiological role they play in thalamic oscillations, leads to the conclusion that SNPs in T-channel genes may contribute to neurological disorders characterized by thalamocortical dysrhythmia, such as generalized epilepsy.

Keywords: Calcium channels, cloning, electrophysiology, ion channel gating, mutation

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