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首页> 外文期刊>American Journal of Physiology >Modulation of the Kir7.1 potassium channel by extracellular and intracellular pH
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Modulation of the Kir7.1 potassium channel by extracellular and intracellular pH

机译：细胞外和细胞内pH对Kir7.1钾通道的调节

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First published December 19, 2007; doi: 10.1152/ajpceU.00393.2007.-Inwardly rectifying K+ (Kir) channels in the apical membrane of the retinal pigment epithelium (RPE) contribute to extracellular K+ homeostasis in the distal retina by mediating K+ secretion. Multiple lines of evidence suggest that these channels are composed of Kir7.1. Previously, we showed that native Kir channels in bovine RPE are modulated by changes in intracellular pH in the physiological range. In the present study, we used the Xenopus laevis oocyte expression system to investigate the pH dependence of cloned human Kir7.1 channels and several point mutants involving histidine residues in the NH2 and COOH termini. Kir7.1 channels were inhibited by strong extracellular acidification and modulated by intracellular pH in a biphasic manner, with maximal activity at about intracellular pH (pHL) 7.0 and inhibition by acidification or alkalinization. Replacement of histidine 26 (H26) in the NH2 terminus with alanine eliminated the requirement of protons for channel activity and increased sensitivity to proton-induced inhibition, resulting in maximal channel activity at alkaline pHi and smaller whole cell currents at resting pHi compared with wild-type Kir7.1. When H26 was replaced with arginine, the pHi sensitivity profile was similar to that of the H26A mutant but with the pKa shifted to a more acidic value, giving rise to whole cell current amplitude at resting pHi that was comparable to that of wild-type Kir7.1. These results indicate that Kir7.1 channels are modulated by intracellular protons by diverse mechanisms and suggest that H26 is important for channel activation at physiological pHj and that it influences an unidentified proton-induced inhibitory mechanism.
机译：首次发布于2007年12月19日; doi：10.1152 / ajpceU.00393.2007.-向内矫正视网膜色素上皮（RPE）顶膜中的K +（Kir）通道，通过介导K +分泌促进远端视网膜中的细胞外K +稳态。多条证据表明这些通道由Kir7.1组成。以前，我们显示了牛RPE中的天然Kir通道受到生理范围内细胞内pH值变化的调节。在本研究中，我们使用非洲爪蟾卵母细胞表达系统来研究克隆的人Kir7.1通道和几个在NH2和COOH末端涉及组氨酸残基的点突变体的pH依赖性。 Kir7.1通道受到强烈的细胞外酸化抑制，并以两相方式受到细胞内pH的调节，在约细胞内pH（pHL）7.0时具有最大活性，并被酸化或碱化抑制。与丙氨酸相比，用丙氨酸替代NH2末端的组氨酸26（H26）消除了质子对通道活性的需求，并增加了对质子诱导的抑制的敏感性，从而导致在碱性pHi下最大的通道活性和在静置pHi下的较小全细胞电流（与野生型相比）。输入Kir7.1。当用精氨酸替代H26时，pHi敏感性特征与H26A突变体相似，但pKa移至更酸性的值，在静止pHi时的全细胞电流幅度与野生型Kir7相当.1。这些结果表明，Kir7.1通道通过多种机制被细胞内质子调节，并且表明H26对于在生理pHj处的通道激活很重要，并且它影响未知的质子诱导的抑制机制。

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