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非洲爪蟾卵母细胞中表达的单个HERG延迟整流钾通道。

Single HERG delayed rectifier K+ channels expressed in Xenopus oocytes.

作者信息

Zou A, Curran M E, Keating M T, Sanguinetti M C

机构信息

Cardiology Division, University of Utah Health Sciences Center, Salt Lake City 84132, USA.

出版信息

Am J Physiol. 1997 Mar;272(3 Pt 2):H1309-14. doi: 10.1152/ajpheart.1997.272.3.H1309.

Abstract

HERG is a K+ channel with properties similar to the rapidly activating component (I(Kr)) of delayed rectifier K+ current, which is important for repolarization of human cardiac myocytes. In this study, we have characterized the single-channel properties of HERG expressed in Xenopus oocytes. Currents were measured in cell-attached patches with an extracellular K concentration of 120 mM. The single HERG channel conductance, determined at test potentials between -50 and -110 mV, was 12.1 +/- 0.6 pS. At positive test potentials (+40 to +80 mV), the probability of channel opening was low and slope conductance was 5.1 +/- 0.6 pS. The mean channel open times at -90 mV were 2.9 +/- 0.5 and 11.8 +/- 1.0 ms, and the mean channel closed times were 0.54 +/- 0.02 and 14.5 +/- 5.3 ms. Single HERG channels were blocked by MK-499, a class III antiarrhythmic agent that blocks I(Kr) in cardiac myocytes. The development of block was more rapid in inside-out patches than in cell-attached patches or in whole cell recordings, indicating that block occurs from the cytoplasmic side of the membrane. The single-channel properties of HERG are similar to I(Kr) channels of isolated cardiac myocytes, which provides further evidence that HERG proteins coassemble to form I(Kr) channels.

摘要

HERG是一种钾离子通道,其特性类似于延迟整流钾电流的快速激活成分(I(Kr)),这对人类心肌细胞的复极化很重要。在本研究中,我们对非洲爪蟾卵母细胞中表达的HERG的单通道特性进行了表征。在细胞贴附式膜片钳记录中,胞外钾浓度为120 mM时测量电流。在-50至-110 mV的测试电位下测定的单个HERG通道电导为12.1±0.6 pS。在正测试电位(+40至+80 mV)下,通道开放概率较低,斜率电导为5.1±0.6 pS。在-90 mV时,平均通道开放时间分别为2.9±0.5和11.8±1.0 ms,平均通道关闭时间分别为0.54±0.02和14.5±5.3 ms。单个HERG通道被MK-499阻断,MK-499是一种III类抗心律失常药物,可阻断心肌细胞中的I(Kr)。在膜内面向外式膜片钳记录中,阻断的发展比细胞贴附式膜片钳记录或全细胞记录更快,表明阻断发生在膜的细胞质侧。HERG的单通道特性与分离的心肌细胞的I(Kr)通道相似,这进一步证明HERG蛋白共同组装形成I(Kr)通道。

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