更新于：2024-05-01

KCNK4

potassium two pore domain channel subfamily K member 4

更新于：2024-05-01

基本信息

别名

K2p4.1、KCNK4、Potassium channel subfamily K member 4

+ [7]

简介

Voltage-insensitive potassium channel (PubMed:22282805). Channel opening is triggered by mechanical forces that deform the membrane (PubMed:22282805, PubMed:25471887, PubMed:25500157, PubMed:30290154). Channel opening is triggered by raising the intracellular pH to basic levels (By similarity). The channel is inactive at 24 degrees Celsius (in vitro); raising the temperature to 37 degrees Celsius increases the frequency of channel opening, with a further increase in channel activity when the temperature is raised to 42 degrees Celsius (By similarity). Plays a role in the perception of pain caused by heat (By similarity). Plays a role in the sensory perception of pain caused by pressure (By similarity).

关联

100 项与 KCNK4 相关的临床结果

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100 项与 KCNK4 相关的转化医学

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0 项与 KCNK4 相关的专利（医药）

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222

项与 KCNK4 相关的文献（医药）

2023-11-07·Proceedings of the National Academy of Sciences of the United States of America

A mechano- and heat-gated two-pore domain K⁺ channel controls excitability in adult zebrafish skeletal muscle.

Article

作者: Romane Idoux ; Chloé Exbrayat-Héritier ; Frédéric Sohm ; Francisco Jaque-Fernandez ; Elisabeth Vaganay ; Christine Berthier ; Sandrine Bretaud ; Vincent Jacquemond ; Florence Ruggiero ; Bruno Allard

TRAAK channels are mechano-gated two-pore-domain K⁺ channels. Up to now, activity of these channels has been reported in neurons but not in skeletal muscle, yet an archetype of tissue challenged by mechanical stress. Using patch clamp methods on isolated skeletal muscle fibers from adult zebrafish, we show here that single channels sharing properties of TRAAK channels, i.e., selective to K⁺ ions, of 56 pS unitary conductance in the presence of 5 mM external K⁺, activated by membrane stretch, heat, arachidonic acid, and internal alkaline pH, are present in enzymatically isolated fast skeletal muscle fibers from adult zebrafish. The kcnk4b transcript encoding for TRAAK channels was cloned and found, concomitantly with activity of mechano-gated K⁺ channels, to be absent in zebrafish fast skeletal muscles at the larval stage but arising around 1 mo of age. The transfer of the kcnk4b gene in HEK cells and in the adult mouse muscle, that do not express functional TRAAK channels, led to expression and activity of mechano-gated K⁺ channels displaying properties comparable to native zebrafish TRAAK channels. In whole-cell voltage-clamp and current-clamp conditions, membrane stretch and heat led to activation of macroscopic K⁺ currents and to acceleration of the repolarization phase of action potentials respectively, suggesting that heat production and membrane deformation associated with skeletal muscle activity can control muscle excitability through TRAAK channel activation. TRAAK channels may represent a teleost-specific evolutionary product contributing to improve swimming performance for escaping predators and capturing prey at a critical stage of development.

2023-11-06·BMJ case reports

KCNK4-related channelopathy causing a neurodevelopmental syndrome.

Article

作者: Ria Garg ; Joseph Sullivan ; David Blair ; Robert Wallerstein

2023-10-10·The journal of physical chemistry. B

Modulation of Mechanosensitive Potassium Channels by a Membrane-targeted Nongenetic Photoswitch.

Article

作者: Matteo Moschetta ; Vito Vurro ; Valentina Sesti ; Chiara Bertarelli ; Giuseppe Maria Paternò ; Guglielmo Lanzani

Mechanosensitive ion channels are present in the plasma membranes of all cells. They play a fundamental role in converting mechanical stimuli into biochemical signals and are involved in several physiological processes such as touch sensation, hearing, and blood pressure regulation. This protein family includes TWIK-related arachidonic acid-stimulated K⁺ channel (TRAAK), which is specifically implicated in the maintenance of the resting membrane potential and in the regulation of a variety of important neurobiological functions. Dysregulation of these channels has been linked to various diseases, including blindness, epilepsy, cardiac arrhythmia, and chronic pain. For these reasons, mechanosensitive channels are targets for the treatment of several diseases. Here, we propose a new approach to investigate TRAAK ion channel modulation that is based on nongenetic photostimulation. We employed an amphiphilic azobenzene, named Ziapin2. In the dark, Ziapin2 preferentially dwells in the plasma membrane, causing a thinning of the membrane. Upon light irradiation, an isomerization occurs, breaking the dimers and inducing membrane relaxation. To study the effect of Ziapin2 on the mechanosensitive channels, we expressed human TRAAK (hTRAAK) channels in HEK293T cells. We observed that Ziapin2 insertion in the membrane is able per se to recruit hTRAAK, permitting the exit of K⁺ ions outside the cells with a consequent hyperpolarization of the cell membrane. During light stimulation, membrane relaxation induces hTRAAK closure, generating a consistent and compensatory depolarization. These results add information to the Ziapin2 mechanism and suggest that membrane deformation can be a tool for the nonselective modulation of mechanosensitive channels.

项与 KCNK4 相关的新闻（医药）

2023-12-27

·生物探索

JCI | 西南医科大学曾博团队发现机械敏感通道TMEM63A和TMEM63B介导肺扩张诱导的表面活性剂分泌

肺表面活性物质是一种附着在肺泡表面的脂蛋白复合物，其作用是降低肺泡表面张力，促进吸气。表面活性物质缺乏常见于早产儿，也见于呼吸窘迫综合征的儿童和成人。肺泡2型上皮(AT2)细胞在肺扩张过程中的机械拉伸是刺激表面活性剂分泌的主要生理因素；然而，目前尚不清楚是否有专门用于这一过程的机械传感器。2023年12月21日，西南医科大学曾博团队在Journal of Clinical Investigation 在线发表题为“Mechanosensitive channels TMEM63A and TMEM63B mediate lung inflation-induced surfactant secretion”的研究论文，该研究表明机械敏感通道TMEM63A和TMEM63B的缺失导致小鼠由于表面活性剂分泌不足而导致肺不张和呼吸衰竭。TMEM63A/B主要定位于板层体的限制膜，这是一种溶酶体相关的细胞器，在AT2细胞中储存肺表面活性物质和ATP。在细胞拉伸过程中，TMEM63A/B通道被激活，促进了与质膜融合的片状体释放表面活性剂和ATP。释放的ATP在AT2细胞中激活Ca2+信号，并增强更多板层体的胞外融合。该研究揭示了TMEM机械敏感通道的重要生理功能，使肺部为出生时的第一次呼吸做好准备，并在一生中维持呼吸。肺表面活性物质是降低肺泡衬里液体表面张力和有效吸气所必需的。肺表面活性物质缺乏导致早产儿新生儿呼吸窘迫综合征，并涉及成人各种肺部疾病，包括急性呼吸窘迫综合征、阻塞性肺疾病、急性呼吸窘迫综合征。众所周知，肺泡上皮细胞(AECs)通过机械敏感的ATP释放和Ca2+依赖途径刺激肺表面活性剂的分泌。AECs由大而薄的肺泡1型(AT1)细胞组成，用于气体交换，立方肺泡2型(AT2)细胞用于合成和分泌肺表面活性剂。在AT2细胞中，肺表面活性剂和ATP储存在板层体(LBs)中，这是一种与溶酶体相关的特化细胞器。肺扩张诱导表面活性剂分泌的一个普遍接受的机制是，AECs的拉伸引起ATP释放到肺泡表面，然后这些释放的ATP在AT2细胞中引起Ca2+信号，促进LBs与质膜的融合和表面活性剂的胞外分泌。然而，仍有几个关键问题尚未解决：(i)机械拉伸如何诱导ATP释放？体外研究表明AT1和AT2细胞都是ATP的来源，ATP释放的途径尚未得到一致的说明。(ii)为什么ATP处理可以有效地刺激LB与质膜融合，但在促进表面活性剂释放方面却远不如细胞拉伸？目前尚不清楚的是，拉伸诱导的Ca2+信号仅仅是P2嘌呤能受体对细胞外ATP的反应，还是含有由细胞拉伸直接激活的Ca2+可渗透机械敏感通道所贡献的成分。机理模式图（图源自Journal of Clinical Investigation ）为了解决这些问题，最重要的问题是了解机械拉伸是如何在AECs中感知和转导的。尚不清楚AECs中是否有一个主要的机械传感器来启动或控制ATP和表面活性剂的释放。在各种能够感知机械力的细胞结构和蛋白质中，机械敏感离子通道与Ca2+信号传导和胞吐作用最为相关。目前，只有四种类型的哺乳动物离子通道通常被认为是真正的机械激活通道，包括Piezo1/2，双孔域K+通道(K2P, TREK/TRAAK)，跨膜通道样TMC1/2和跨膜63 (TMEM63)通道。尽管在AT1细胞系中发现Piezo1可以调节ATP释放，但在小鼠肺中未检测到其在AECs中的功能表达。K2P通道广泛表达，但由于其复极化作用，与Ca2+信号没有直接关系。TMC1/2在耳蜗毛细胞中形成机械转导通道，其突变仅导致听力损失。作为最近发现的机械敏感通道，TMEM63B在毛细胞存活中起关键作用，对听力至关重要，但TMEM63A/B/C在其他系统中的生理功能尚不清楚。综上所述，该研究发现AT2细胞中的TMEM63A/B机械敏感通道通过感知和转导肺泡扩张过程中LBs所受的机械力来控制肺表面活性剂和ATP的释放。TMEM63A/B 缺乏导致肺泡表面活性物质不足，进而引起肺不张和呼吸衰竭。该研究证明了机械敏感通道TMEM63A和TMEM63B是AECs中的机械传感器，介导肺扩张诱导的表面活性剂和ATP的释放，并在维持呼吸功能中发挥重要作用。参考文献:Chen GL, Li JY, Chen X, Liu JW, et al. Mechanosensitive channels TMEM63A and TMEM63B mediate lung inflation-induced surfactant secretion. J Clin Invest. 2023 Dec 21:e174508. doi: 10.1172/JCI174508. Epub ahead of print. PMID: 38127458.文章来源：“iNature”责编|探索君排版|探索君End往期精选围观王晓红教授团队：绘制单次冷冻囊胚移植成功的女性植入期外周血microRNA动态表达谱，开拓领域创新研究热文维生素B12在细胞重编程与组织再生中发挥关键作用！热文不孕症治疗新方向！又一导致女性不孕的关键因素被发现热文Let-7家族miRNA或为癌症潜在免疫治疗靶点热文一项最新发现或可用于阿尔茨海默病药物开发点击“阅读原文”，了解更多~

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