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肠道起搏细胞中的内向整流氯通道活性

Inwardly rectifying chloride channel activity in intestinal pacemaker cells.

作者信息

Zhu Yaohui, Mucci Andrea, Huizinga Jan D

机构信息

McMaster Univ., HSC-3N5C, 1200 Main St. West, Hamilton, ON L8N 3Z5, Canada.

出版信息

Am J Physiol Gastrointest Liver Physiol. 2005 Apr;288(4):G809-21. doi: 10.1152/ajpgi.00301.2004. Epub 2004 Nov 4.

DOI:10.1152/ajpgi.00301.2004
PMID:15528256
Abstract

Cl(-) channels are proposed to play a role in gut pacemaker activity, but little is known about the characteristics of Cl(-) channels in interstitial cells of Cajal (ICC), the intestinal pacemaker cells. The objective of the present study was to identify whole cell Cl(-) currents in ICC associated with previously observed single-channel activity and to characterize its inward rectification. Whole cell patch-clamp studies showed that ICC express an inwardly rectifying Cl(-) current that was not sensitive to changes in cation composition of the extracellular solutions. Currents were not affected by replacing all cations with N-methyl-d-glucamine (NMDG(+)). Whole cell currents followed the Cl(-) equilibrium potential and were inhibited by DIDS and 9-anthracene carboxylic acid. Ramp protocols of single-channel activity showed that inward rectification was due to reduction in single-channel open probability, not a reduction in single-channel conductance. Single-channel data led to the hypothesis that strong cooperation exists between 30-pS channels that show less cooperation at potentials positive to the reversal potential. Hence, an inwardly rectifying Cl(-) channel plays a prominent role in determining pacemaker activity in the gut.

摘要

氯离子通道被认为在肠道起搏器活动中发挥作用,但对于肠道起搏器细胞即 Cajal 间质细胞(ICC)中氯离子通道的特性却知之甚少。本研究的目的是识别 ICC 中与先前观察到的单通道活动相关的全细胞氯离子电流,并对其内向整流特性进行表征。全细胞膜片钳研究表明,ICC 表达一种内向整流的氯离子电流,该电流对细胞外溶液阳离子组成的变化不敏感。用 N - 甲基 - D - 葡萄糖胺(NMDG⁺)替代所有阳离子时,电流不受影响。全细胞电流遵循氯离子平衡电位,并被二硝基苯磺酸(DIDS)和 9 - 蒽甲酸抑制。单通道活动的斜坡方案表明,内向整流是由于单通道开放概率降低,而非单通道电导降低。单通道数据引出了这样一个假说:在 30 - pS 通道之间存在强协同作用,而在正于反转电位的电位下这种协同作用较弱。因此,一种内向整流的氯离子通道在决定肠道起搏器活动中起着重要作用。

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