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电压门控钾通道作为治疗神经和精神疾病的潜在治疗靶点。

Voltage-gated potassium channels as a potential therapeutic target for the treatment of neurological and psychiatric disorders.

作者信息

Faulkner Isabel E, Pajak Rachael Z, Harte Michael K, Glazier Jocelyn D, Hager Reinmar

机构信息

Division of Evolution, Infection and Genomics, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United Kingdom.

Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United Kingdom.

出版信息

Front Cell Neurosci. 2024 Oct 1;18:1449151. doi: 10.3389/fncel.2024.1449151. eCollection 2024.

DOI:10.3389/fncel.2024.1449151
PMID:39411003
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11473391/
Abstract

Voltage-gated potassium channels are a widely distributed subgroup of potassium channels responsible for the efflux of potassium in the repolarisation of the cell membrane, and hence contribute to the latency and propagation of action potentials. As they are causal to synaptic transmission, alterations to the structure of these channels can lead to a variety of neurological and psychiatric diseases. The Kv3 subfamily of voltage-gated potassium channels are found on many neurons in the brain, including inhibitory interneurons where they contribute to fast-frequency firing. Changes to the firing ability of these interneurons can lead to an imbalance of inhibitory and excitatory neurotransmission. To date, we have little understanding of the mechanism by which excitatory and inhibitory inputs become imbalanced. This imbalance is associated with cognitive deficits seen across neurological and neuropsychiatric disorders, which are currently difficult to treat. In this review, we collate evidence supporting the hypothesis that voltage-gated potassium channels, specifically the Kv3 subfamily, are central to many neurological and psychiatric disorders, and may thus be considered as an effective drug target. The collective evidence provided by the studies reviewed here demonstrates that Kv3 channels may be amenable to novel treatments that modulate the activity of these channels, with the prospect of improved patient outcome.

摘要

电压门控钾通道是钾通道中分布广泛的一个亚组,负责细胞膜复极化过程中钾离子的外流,因此对动作电位的潜伏期和传播有影响。由于它们对突触传递至关重要,这些通道结构的改变会导致多种神经和精神疾病。电压门控钾通道的Kv3亚家族存在于大脑中的许多神经元上,包括抑制性中间神经元,它们在这些神经元中有助于快速频率放电。这些中间神经元放电能力的改变会导致抑制性和兴奋性神经传递失衡。迄今为止,我们对兴奋性和抑制性输入失衡的机制了解甚少。这种失衡与多种神经和神经精神疾病中出现的认知缺陷有关,而这些疾病目前难以治疗。在这篇综述中,我们整理了支持以下假设的证据:电压门控钾通道,特别是Kv3亚家族,在许多神经和精神疾病中起核心作用,因此可能被视为一个有效的药物靶点。本文综述的研究提供的综合证据表明,Kv3通道可能适用于调节这些通道活性的新治疗方法,有望改善患者预后。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc00/11473391/89444613fc88/fncel-18-1449151-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc00/11473391/b6a27ea74d33/fncel-18-1449151-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc00/11473391/89444613fc88/fncel-18-1449151-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc00/11473391/b6a27ea74d33/fncel-18-1449151-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc00/11473391/89444613fc88/fncel-18-1449151-g002.jpg

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