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钾通道调节脑动脉中的电信号传导。

K channels tune electrical communication in cerebral arteries.

作者信息

Sancho Maria, Samson Nina C, Hald Bjorn O, Hashad Ahmed M, Marrelli Sean P, Brett Suzanne E, Welsh Donald G

机构信息

1 Department of Physiology and Pharmacology, University of Western Ontario, London, Canada.

2 Department of Physiology and Pharmacology, Hotchkiss Brain Institute, Libin Cardiovascular Institute, University of Calgary, Calgary, Canada.

出版信息

J Cereb Blood Flow Metab. 2017 Jun;37(6):2171-2184. doi: 10.1177/0271678X16662041. Epub 2016 Jan 1.

Abstract

The conducted vasomotor response reflects electrical communication in the arterial wall and the distance signals spread is regulated by three factors including resident ion channels. This study defined the role of inward-rectifying K channels (K) in governing electrical communication along hamster cerebral arteries. Focal KCl application induced a vasoconstriction that conducted robustly, indicative of electrical communication among cells. Inhibiting dominant K conductances had no attenuating effect, the exception being Ba blockade of K. Electrophysiology and Q-PCR analysis of smooth muscle cells revealed a Ba-sensitive K current comprised of K2.1/2.2 subunits. This current was surprisingly small and when incorporated into a model, failed to account for the observed changes in conduction. We theorized a second population of K channels exist and consistent with this idea, a robust Ba-sensitive K2.1/2.2 current was observed in endothelial cells. When both K currents were incorporated into, and then inhibited in our model, conduction decay was substantive, aligning with experiments. Enhanced decay was ascribed to the rightward shift in membrane potential and the increased feedback arising from voltage-dependent-K channels. In summary, this study shows that two K populations work collaboratively to govern electrical communication and the spread of vasomotor responses along cerebral arteries.

摘要

所进行的血管运动反应反映了动脉壁中的电信号传导,而信号传播的距离受包括驻留离子通道在内的三个因素调节。本研究确定了内向整流钾通道(K)在控制仓鼠脑动脉电信号传导中的作用。局部应用氯化钾可诱导强烈的血管收缩,这表明细胞间存在电信号传导。抑制主要的钾电导没有减弱作用,但钡对K的阻断除外。平滑肌细胞的电生理学和定量聚合酶链反应分析显示,一种由K2.1/2.2亚基组成的钡敏感钾电流。该电流出奇地小,当纳入模型时,无法解释观察到的传导变化。我们推测存在第二种钾通道群体,与此观点一致的是,在内皮细胞中观察到了强大的钡敏感K2.1/2.2电流。当将两种钾电流都纳入我们的模型并对其进行抑制时,传导衰减显著,这与实验结果相符。衰减增强归因于膜电位的右移以及电压依赖性钾通道产生的反馈增加。总之,本研究表明,两种钾通道群体协同作用,控制电信号传导以及血管运动反应在脑动脉中的传播。

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