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Kv7 通道与兴奋性紊乱。

Kv7 Channels and Excitability Disorders.

机构信息

Faculty of Biological Sciences, University of Leeds, Leeds, UK.

Department of Pharmacology, Hebei Medical University, Shijiazhuang, China.

出版信息

Handb Exp Pharmacol. 2021;267:185-230. doi: 10.1007/164_2021_457.

Abstract

Kv7.1-Kv7.5 (KCNQ1-5) K channels are voltage-gated K channels with major roles in neurons, muscle cells and epithelia where they underlie physiologically important K currents, such as neuronal M current and cardiac I. Specific biophysical properties of Kv7 channels make them particularly well placed to control the activity of excitable cells. Indeed, these channels often work as 'excitability breaks' and are targeted by various hormones and modulators to regulate cellular activity outputs. Genetic deficiencies in all five KCNQ genes result in human excitability disorders, including epilepsy, arrhythmias, deafness and some others. Not surprisingly, this channel family attracts considerable attention as potential drug targets. Here we will review biophysical properties and tissue expression profile of Kv7 channels, discuss recent advances in the understanding of their structure as well as their role in various neurological, cardiovascular and other diseases and pathologies. We will also consider a scope for therapeutic targeting of Kv7 channels for treatment of the above health conditions.

摘要

Kv7.1-Kv7.5 (KCNQ1-5) 钾通道是电压门控钾通道,在神经元、肌肉细胞和上皮细胞中具有重要作用,它们是生理上重要的钾电流的基础,如神经元 M 电流和心脏 I 电流。Kv7 通道的特定生物物理特性使它们特别适合控制可兴奋细胞的活性。事实上,这些通道通常作为“兴奋性阻断”,并被各种激素和调节剂靶向,以调节细胞活动输出。五个 KCNQ 基因的全部缺失导致人类兴奋性障碍,包括癫痫、心律失常、耳聋和其他一些疾病。毫不奇怪,这个通道家族作为潜在的药物靶点引起了相当大的关注。在这里,我们将回顾 Kv7 通道的生物物理特性和组织表达谱,讨论它们结构的最新进展,以及它们在各种神经、心血管和其他疾病和病理中的作用。我们还将考虑针对 Kv7 通道进行治疗的治疗靶点,以治疗上述健康状况。

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