摘要
低电压T型钙通道广泛分布在各种类型细胞中,包括心血管和神经元细胞中,与高电压钙通道不同,在接近膜静息电位的低度去极化时即能被激活,因而有利于心脏起博和神经元细胞在生理状态下接近静息时,对兴奋和电反应的调节。但对T型钙通道在疾病中的作用所知有限。近年来因为克隆出3种T型钙通道α1亚单位的基因,(Cav3.1,Cav3.2和Cav3.3),使深入研究实验动物及人体疾病时T型钙通道的性质、药理、体内分布、基因调节成为可能。并且为新药研发提供有力工具。转基因动物实验已证明T型钙通道不仅是治疗肾性高血压、心律失常也是治疗意识丧失型癫痫及神经性疼痛的重要药物靶点。此外,细胞内钙超载还与房颤、心衰、偏头痛、阿尔采末病、睡眠障碍等的发病有关,所以盼望有新的T型钙通道阻断剂出现。有报道Efonidipine能选择性地抑制低电压T型钙通道,有望成为选择性阻断剂。此外,近年来调控T型钙通道活性的分子机制的研究取得新的达展,对新药的开发有所启迪。作者建议,对治疗心血管及神经系统疾病的药物靶点T型钙通道及其阻断剂的研究给予更多的关注。
Low-voltage-activated calcium channels（Cav3.2 Ttype calcium channels） are widely expressed in different type of cells including cardiovascular cells and neurons.In contrast to high-voltage-activated calcium channels,T-type channels can be activated by a weak depolarization near the resting membrane potential once deinactivated by hyperpolarization,and therefore can regulate the excitability and electroresponsiveness of cells under physiological conditions near resting states.But there has been limited understanding about the role of T-type calcium channels played in diseases.Recently,the molecular cloning of the three T-channel gene（Cav3.1,Cav3.2 and Cav3.3） has allowed detailed studies of channel properties,pharmacology,distribution in different cells,up-regulation in animal models of disease or patients,and has provided the tools to screen for novel drugs.Studies of transgenic animals have provided the proof-of-concept that T-channels are important drug targets for the treatment of glomerular hypertension,arrhythmia,absence epilepsy and neuropathic pain.T-channel gene mutations have been found in patients with childhood absence epilepsy.Moreover,cellular calcium overload also related to pathogenesis of atrial fibrillation,congestive heart failure,migraine,Alzheimer＇s disease,sleep disorder and so on.Therefore new Ca2 ＋ channel antagonists are expected.It was found that R（-） efonidipine selectely inhibited only low-voltage activated T-type Ca2 ＋ channels.Investigations were carried out about the cellular mechanisms that control T-type channel activity recently,and may be useful for drug exploitation.Authors suggest that more attention should be paid to the investigation of T-channels and it＇s antagonists,as well as the novel important drug targets for the treatment of cardiovascular and nervous system diseases.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2010年第9期1250-1253,共4页
Chinese Pharmacological Bulletin
关键词
T型钙通道
调控
阻断剂
体内分布
心血管疾病
神经系统疾病
T-type Ca2 ＋ channels
regulation
antagonist
distribution
cardiovascular diseases
nervous system diseases
