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T型钙通道的分子生物学

Molecular biology of T-type calcium channels.

作者信息

Perez-Reyes E, Lory P

机构信息

Departments of Pharmacology, University of Virginia, Charlottesville, VA 22908, USA.

出版信息

CNS Neurol Disord Drug Targets. 2006 Dec;5(6):605-9. doi: 10.2174/187152706779025508.

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 alpha1 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.

摘要

本综述总结了低电压门控T型钙通道分子生物学的最新进展。编码这些通道的基因是通过对与高电压激活Ca2+通道的α1亚基序列相似的cDNA进行分子克隆而鉴定出来的。鉴定出了三个T通道基因:编码Cav3.1的CACNA1G、编码Cav3.2的CACNA1H以及编码Cav3.3的CACNA1I。最近的研究集中在这些基因如何产生可变剪接转录本,以及这种剪接如何影响通道活性。另一个关注领域是单核苷酸多态性(SNP)如何改变通道活性。基于它们在丘脑核中的分布,再结合它们在丘脑振荡中所起的生理作用,得出结论:T通道基因中的SNP可能导致以丘脑皮质节律紊乱为特征的神经系统疾病,如全身性癫痫。

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