Effect of external pH on activation of the Kv1.5 potassium channel.
Effect of external pH on activation of the Kv1.5 potassium channel.
复制标题
DOI：
10.1016/s0006-3495(03)74842-5
复制
发表时间：
2003
影响因子：
3.4
通讯作者：
Josef G. Trapani;S. Korn
中科院分区：
文献类型：
--
作者：
Josef G. Trapani;S. Korn
我们研究了从pH 7.3到6.8的外部酸化降低Kv1.5钾通道电流幅度的机制。在生理外加[K+]时，激活电压依赖性的改变是酸化引起的Kv1.5电流幅度降低的完全原因(pK=7.15)。外加[Ca~(2+)]或[Mg~(2+)]的升高使活化曲线右移，活化曲线的pH敏感性向更酸性的值移动。对Kv2.1K+通道也进行了类似的观察，只是激活位移的pk超出了生理范围。这些数据与酸化通过改变局部表面电位而改变活化的机制是一致的。在pH 7.3或更高时，消除传导通路外前庭内的8个正电荷对激活的电压依赖性没有影响，这表明暴露于传导通路内的部位并不直接对相关的局部表面电位有贡献。然而，487位(传导通路内)的突变取代了激活中对pH敏感的变化的PK，从而降低或消除了Kv1.5电流对与生理相关的pH变化的敏感性。这些结果表明，在电压门控K+通道中，Kv1.5中的激活对与生理相关的pH变化是唯一敏感的，因为引起局部表面电位效应的位点的pK接近于pH 7。此外，激活位移的pK不仅取决于所涉及的位点的性质，而且部分地取决于传导途径中至少一个残基所赋予的结构取向。
We studied the mechanism by which external acidification from pH 7.3 to 6.8 reduced current magnitude in the Kv1.5 potassium channel. At physiological external [K+], a shift in the voltage-dependence of activation was entirely responsible for the acidification-induced decrease in Kv1.5 current magnitude (pK=7.15). Elevation of external [Ca2+] or [Mg2+] identically shifted activation curves to the right and identically shifted the pH-sensitivity of the activation curves to more acidic values. Similar observations were made with the Kv2.1K+channel, except that the pK for the activation shift was out of the physiological range. These data are consistent with a mechanism by which acidification shifted activation via modification of a local surface potential. Elimination of eight positive charges within the outer vestibule of the conduction pathway had no effect on the voltage-dependence of activation at pH 7.3 or higher, which suggested that sites exposed to the conduction pathway within the outer vestibule did not directly contribute to the relevant local surface potential. However, mutations at position 487 (within the conduction pathway) displaced the pK of the pH-sensitive shift in activation, such that the sensitivity of Kv1.5 current to physiologically relevant changes in pH was reduced or eliminated. These results suggest that, among voltage-gated K+channels, activation in Kv1.5 is uniquely sensitive to physiologically relevant changes in pH because the pK for the sites that contribute to the local surface potential effect is near pH 7. Moreover, the pK for the activation shift depends not only on the nature of the sites involved but also on structural orientation conferred, in part, by at least one residue within the conduction pathway.