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

IF 4.2 3区 医学 Q2 NEUROSCIENCES
Frontiers in Cellular Neuroscience Pub Date : 2024-10-01 eCollection Date: 2024-01-01 DOI:10.3389/fncel.2024.1449151
Isabel E Faulkner, Rachael Z Pajak, Michael K Harte, Jocelyn D Glazier, Reinmar Hager
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引用次数: 0

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.

电压门控钾通道是治疗神经和精神疾病的潜在治疗靶点。
电压门控钾通道是钾通道中分布广泛的一个亚群,负责细胞膜再极化过程中钾的外流,因此有助于动作电位的潜伏期和传播。由于它们对突触传递起着重要作用,这些通道结构的改变可导致多种神经和精神疾病。Kv3 亚家族电压门控钾通道存在于大脑中的许多神经元上,包括抑制性中间神经元,它们在这些神经元上对快频点火做出了贡献。这些中间神经元发射能力的变化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还知之甚少。这种失衡与神经和神经精神疾病中的认知缺陷有关,目前难以治疗。在这篇综述中,我们整理了支持这一假设的证据:电压门控钾通道,特别是 Kv3 亚家族,是许多神经和精神疾病的核心,因此可被视为有效的药物靶点。本文所综述的研究提供的集体证据表明,Kv3 通道可能适用于调节这些通道活性的新型疗法,从而有望改善患者的预后。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
7.90
自引率
3.80%
发文量
627
审稿时长
6-12 weeks
期刊介绍: Frontiers in Cellular Neuroscience is a leading journal in its field, publishing rigorously peer-reviewed research that advances our understanding of the cellular mechanisms underlying cell function in the nervous system across all species. Specialty Chief Editors Egidio D‘Angelo at the University of Pavia and Christian Hansel at the University of Chicago are supported by an outstanding Editorial Board of international researchers. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.
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