Rajakulendran Sanjeev, Hanna Michael G
UCL-Institute of Neurology, MRC Centre for Neuromuscular Diseases, Queen Square, London WC1N 3BG, United Kingdom.
Cold Spring Harb Perspect Med. 2016 Jan 4;6(1):a022723. doi: 10.1101/cshperspect.a022723.
A central theme in the quest to unravel the genetic basis of epilepsy has been the effort to elucidate the roles played by inherited defects in ion channels. The ubiquitous expression of voltage-gated calcium channels (VGCCs) throughout the central nervous system (CNS), along with their involvement in fundamental processes, such as neuronal excitability and synaptic transmission, has made them attractive candidates. Recent insights provided by the identification of mutations in the P/Q-type calcium channel in humans and rodents with epilepsy and the finding of thalamic T-type calcium channel dysfunction in the absence of seizures have raised expectations of a causal role of calcium channels in the polygenic inheritance of idiopathic epilepsy. In this review, we consider how genetic variation in neuronal VGCCs may influence the development of epilepsy.
在探索癫痫遗传基础的过程中,一个核心主题是努力阐明离子通道遗传缺陷所起的作用。电压门控钙通道(VGCCs)在整个中枢神经系统(CNS)中普遍表达,并且参与诸如神经元兴奋性和突触传递等基本过程,这使其成为有吸引力的研究对象。近期,在患有癫痫的人类和啮齿动物中发现P/Q型钙通道突变,以及在无癫痫发作情况下发现丘脑T型钙通道功能障碍,这些新见解引发了人们对钙通道在特发性癫痫多基因遗传中因果作用的期待。在本综述中,我们探讨神经元VGCCs的遗传变异如何可能影响癫痫的发展。