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TASK,一种人类背景钾离子通道,用于感知生理pH值附近的外部pH变化。

TASK, a human background K+ channel to sense external pH variations near physiological pH.

作者信息

Duprat F, Lesage F, Fink M, Reyes R, Heurteaux C, Lazdunski M

机构信息

Institut de Pharmacologie Moléculaire et Cellulaire, CNRS, 660 route des Lucioles, Sophia Antipolis, 06560 Valbonne, France.

出版信息

EMBO J. 1997 Sep 1;16(17):5464-71. doi: 10.1093/emboj/16.17.5464.

Abstract

TASK is a new member of the recently recognized TWIK K+ channel family. This 395 amino acid polypeptide has four transmembrane segments and two P domains. In adult human, TASK transcripts are found in pancreas<placenta<brain<lung, prostate<heart, kidney<uterus, small intestine and colon. Electrophysiological properties of TASK were determined after expression in Xenopus oocytes and COS cells. TASK currents are K+-selective, instantaneous and non-inactivating. They show an outward rectification when external [K+] is low ([K+]out = 2 mM) which is not observed for high [K+]out (98 mM). The rectification can be approximated by the Goldman-Hodgkin-Katz current equation that predicts a curvature of the current-voltage plot in asymmetric K+ conditions. This strongly suggests that TASK lacks intrinsic voltage sensitivity. The absence of activation and inactivation kinetics as well as voltage independence are characteristic of conductances referred to as leak or background conductances. For this reason, TASK is designated as a background K+ channel. TASK is very sensitive to variations of extracellular pH in a narrow physiological range; as much as 90% of the maximum current is recorded at pH 7.7 and only 10% at pH 6.7. This property is probably essential for its physiological function, and suggests that small pH variations may serve a communication role in the nervous system.

摘要

TASK是最近被认可的TWIK K⁺通道家族的新成员。这条由395个氨基酸组成的多肽有四个跨膜片段和两个P结构域。在成年人体内,TASK转录本存在于胰腺、胎盘、大脑、肺、前列腺、心脏、肾脏、子宫、小肠和结肠中。在非洲爪蟾卵母细胞和COS细胞中表达后,测定了TASK的电生理特性。TASK电流具有K⁺选择性、瞬时性且不发生失活。当外部[K⁺]较低([K⁺]外 = 2 mM)时,它们表现出外向整流,而在高[K⁺]外(98 mM)时未观察到这种情况。这种整流可以用戈德曼-霍奇金- Katz电流方程近似,该方程预测在不对称K⁺条件下电流-电压图的曲率。这强烈表明TASK缺乏内在电压敏感性。缺乏激活和失活动力学以及电压独立性是被称为泄漏或背景电导的电导率的特征。因此,TASK被指定为背景K⁺通道。TASK在狭窄的生理范围内对细胞外pH的变化非常敏感;在pH 7.7时记录到的最大电流高达90%,而在pH 6.7时仅为10%。这种特性可能对其生理功能至关重要,并表明小的pH变化可能在神经系统中起到通讯作用。

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