Astroglial Kir4.1 and AQP4 Channels: Key Regulators of Potassium Homeostasis and Their Implications in Autism Spectrum Disorders.

IF 4.8 4区 医学 Q3 CELL BIOLOGY
Vesal Abbasian, Shima Davoudi, Amin Vahabzadeh, Mohammad Javad Maftoon-Azad, Mahyar Janahmadi
{"title":"Astroglial Kir4.1 and AQP4 Channels: Key Regulators of Potassium Homeostasis and Their Implications in Autism Spectrum Disorders.","authors":"Vesal Abbasian, Shima Davoudi, Amin Vahabzadeh, Mohammad Javad Maftoon-Azad, Mahyar Janahmadi","doi":"10.1007/s10571-025-01574-w","DOIUrl":null,"url":null,"abstract":"<p><p>Astroglial Kir4.1 and AQP4 channels are pivotal regulators of potassium (K<sup>+</sup>) and water homeostasis in the brain, playing essential roles in maintaining neuronal stability, facilitating synaptic transmission, and supporting overall brain function. Kir4.1 channels promote the efficient uptake of K<sup>+</sup> ions from the extracellular space, particularly during periods of high neuronal activity, thereby preventing excessive neuronal excitability-a condition linked to several neurological disorders, including Autism Spectrum Disorder (ASD). Meanwhile, AQP4 channels, predominantly expressed in the astrocytic end-feet at the blood-brain barrier, regulate water transport across cell membranes, ensuring osmotic balance that complements the function of Kir4.1 in K<sup>+</sup> clearance. Recent studies have underscored the critical link between dysfunctions in these channels and the pathophysiology of ASD, a complex neurodevelopmental disorder characterized by a broad range of social, communicative, and behavioral impairments. Mutations or dysregulations in Kir4.1 and AQP4 channels can disrupt K<sup>+</sup> and water homeostasis, exacerbating neuronal hyperexcitability and contributing to hallmark ASD symptoms, such as sensory processing abnormalities, social deficits, and an increased risk of seizures. This review synthesizes current findings, focusing on the molecular mechanisms of Kir4.1 and AQP4 channels, their role in astrocyte-neuron interactions, and their pathophysiological implications in ASD. It also provides a detailed discussion of potential therapeutic interventions targeting these channels to mitigate ASD symptoms.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"45 1","pages":"56"},"PeriodicalIF":4.8000,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12158897/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cellular and Molecular Neurobiology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10571-025-01574-w","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Astroglial Kir4.1 and AQP4 channels are pivotal regulators of potassium (K+) and water homeostasis in the brain, playing essential roles in maintaining neuronal stability, facilitating synaptic transmission, and supporting overall brain function. Kir4.1 channels promote the efficient uptake of K+ ions from the extracellular space, particularly during periods of high neuronal activity, thereby preventing excessive neuronal excitability-a condition linked to several neurological disorders, including Autism Spectrum Disorder (ASD). Meanwhile, AQP4 channels, predominantly expressed in the astrocytic end-feet at the blood-brain barrier, regulate water transport across cell membranes, ensuring osmotic balance that complements the function of Kir4.1 in K+ clearance. Recent studies have underscored the critical link between dysfunctions in these channels and the pathophysiology of ASD, a complex neurodevelopmental disorder characterized by a broad range of social, communicative, and behavioral impairments. Mutations or dysregulations in Kir4.1 and AQP4 channels can disrupt K+ and water homeostasis, exacerbating neuronal hyperexcitability and contributing to hallmark ASD symptoms, such as sensory processing abnormalities, social deficits, and an increased risk of seizures. This review synthesizes current findings, focusing on the molecular mechanisms of Kir4.1 and AQP4 channels, their role in astrocyte-neuron interactions, and their pathophysiological implications in ASD. It also provides a detailed discussion of potential therapeutic interventions targeting these channels to mitigate ASD symptoms.

星形胶质细胞Kir4.1和AQP4通道:钾稳态的关键调节因子及其在自闭症谱系障碍中的意义
星形胶质细胞Kir4.1和AQP4通道是脑内钾(K+)和水稳态的关键调节因子,在维持神经元稳定性、促进突触传递和支持脑整体功能方面发挥重要作用。Kir4.1通道促进细胞外空间对K+离子的有效吸收,特别是在神经元高活动期间,从而防止神经元过度兴奋——一种与包括自闭症谱系障碍(ASD)在内的几种神经系统疾病相关的疾病。同时,主要表达于血脑屏障星形细胞端足的AQP4通道调节水跨细胞膜运输,确保渗透平衡,补充Kir4.1在K+清除中的功能。最近的研究强调了这些通道功能障碍与ASD病理生理学之间的关键联系,ASD是一种复杂的神经发育障碍,其特征是广泛的社交、交流和行为障碍。Kir4.1和AQP4通道的突变或失调可破坏K+和水分稳态,加剧神经元的过度兴奋性,并导致ASD的典型症状,如感觉处理异常、社交缺陷和癫痫发作风险增加。本文综述了目前的研究成果,重点关注Kir4.1和AQP4通道的分子机制,它们在星形细胞-神经元相互作用中的作用,以及它们在ASD中的病理生理意义。它还提供了针对这些通道减轻ASD症状的潜在治疗干预的详细讨论。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
CiteScore
7.70
自引率
0.00%
发文量
137
审稿时长
4-8 weeks
期刊介绍: Cellular and Molecular Neurobiology publishes original research concerned with the analysis of neuronal and brain function at the cellular and subcellular levels. The journal offers timely, peer-reviewed articles that describe anatomic, genetic, physiologic, pharmacologic, and biochemical approaches to the study of neuronal function and the analysis of elementary mechanisms. Studies are presented on isolated mammalian tissues and intact animals, with investigations aimed at the molecular mechanisms or neuronal responses at the level of single cells. Cellular and Molecular Neurobiology also presents studies of the effects of neurons on other organ systems, such as analysis of the electrical or biochemical response to neurotransmitters or neurohormones on smooth muscle or gland cells.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信