心脏细胞中的一种机械敏感钾通道。由花生四烯酸激活。

A mechanosensitive K+ channel in heart cells. Activation by arachidonic acid.

作者信息

Kim D

机构信息

Department of Physiology and Biophysics, Chicago Medical School, Illinois 60064.

出版信息

J Gen Physiol. 1992 Dec;100(6):1021-40. doi: 10.1085/jgp.100.6.1021.

DOI:10.1085/jgp.100.6.1021

PMID:1484283

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2229139/

Abstract

Mechanosensitive ion channels have been described in many types of cells. These channels are believed to transduce pressure signals into intracellular biochemical and physiological events. In this study, the patch-clamp technique was used to identify and characterize a mechanosensitive ion channel in rat atrial cells. In cell-attached patches, negative pressure in the pipette activated an ion channel in a pressure-dependent manner. The pressure to induce half-maximal activation was 12 +/- 3 mmHg at +40 mV, and nearly full activation was observed at approximately 20 mmHg. The probability of opening was voltage dependent, with greater channel activity at depolarized potentials. The mechanosensitive channel was identical to the K+ channel previously shown to be activated by arachidonic acid and other lipophilic compounds, as judged by the outwardly rectifying current-voltage relation, single channel amplitude, mean open time (1.4 +/- 0.3 ms), bursty openings, K+ selectivity, insensitivity to any known organic inhibitors of ion channels, and pH sensitivity. In symmetrical 140 mM KCl, the slope conductance was 94 +/- 11 pS at +60 mV and 64 +/- 8 pS at -60 mV. Anions and cations such as Cl-, glutamate, Na+, Cs+, Li+, Ca2+, and Ba2+ were not permeant. Extracellular Ba2+ (1 mM) blocked the inward K+ current completely. GdCl3 (100 microM) or CaCl2 (100 microM) did not alter the K+ channel activity or amplitude. Lowering of intracellular pH increased the pressure sensitivity of the channel. The K+ channel could be activated in the presence of 5 mM intracellular [ATP] or 10 microM glybenclamide in inside-out patches. In the absence of ATP, when the ATP-sensitive K+ channel was active, the mechanosensitive channel could further be activated by pressure, suggesting that they were two separate channels. The ATP-sensitive K+ channel was not mechanosensitive. Pressure activated the K+ channel in the presence of albumin, a fatty acid binding protein, suggesting that pressure and arachidonic acid activate the K+ channel via separate pathways.

摘要

机械敏感离子通道已在多种类型的细胞中被描述。这些通道被认为可将压力信号转化为细胞内的生化和生理事件。在本研究中，采用膜片钳技术来鉴定和表征大鼠心房细胞中的一种机械敏感离子通道。在细胞贴附式膜片中，移液管内的负压以压力依赖的方式激活一个离子通道。在 +40 mV 时，诱导半数最大激活的压力为 12±3 mmHg，在约 20 mmHg 时观察到近乎完全激活。开放概率依赖于电压，在去极化电位时通道活性更高。根据外向整流电流 - 电压关系、单通道幅度、平均开放时间（1.4±0.3 ms）、爆发式开放、K⁺ 选择性、对任何已知离子通道有机抑制剂不敏感以及 pH 敏感性判断，该机械敏感通道与先前显示可被花生四烯酸和其他亲脂性化合物激活的 K⁺ 通道相同。在对称的 140 mM KCl 中，在 +60 mV 时斜率电导为 94±11 pS，在 -60 mV 时为 64±8 pS。Cl⁻、谷氨酸、Na⁺、Cs⁺、Li⁺、Ca²⁺ 和 Ba²⁺ 等阴离子和阳离子不具有通透性。细胞外 Ba²⁺（1 mM）完全阻断内向 K⁺ 电流。GdCl₃（100 μM）或 CaCl₂（100 μM）不改变 K⁺ 通道活性或幅度。降低细胞内 pH 会增加通道的压力敏感性。在膜内面向外式膜片中，当细胞内 [ATP] 为 5 mM 或格列本脲为 10 μM 时，K⁺ 通道可被激活。在无 ATP 时，当 ATP 敏感 K⁺ 通道活跃时，机械敏感通道可进一步被压力激活，表明它们是两个独立的通道。ATP 敏感 K⁺ 通道不具有机械敏感性。在脂肪酸结合蛋白白蛋白存在的情况下，压力激活了 K⁺ 通道，这表明压力和花生四烯酸通过不同途径激活 K⁺ 通道。