Two pore residues mediate acidosis-induced enhancement of C-type inactivation of the Kv1.4 K+ channel

被引：19

作者：

Claydon, TW ^{[1
]}

Boyett, MR ^{[1
]}

Sivaprasadarao, A ^{[1
]}

Orchard, CH ^{[1
]}

机构：

[1] Univ Leeds, Sch Biomed Sci, Leeds LS2 9JT, W Yorkshire, England

来源：

AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY | 2002年 / 283卷 / 04期

关键词：

acidosis; C-type inactivation; Kv1.4;

D O I：

10.1152/ajpcell.00542.2001

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Acidosis inhibits current through the Kv1.4 K+ channel, perhaps as a result of enhancement of C-type inactivation. The mechanism of action of acidosis on C-type inactivation has been studied. A mutant Kv1.4 channel that lacks N-type inactivation (fKv1.4 Delta2-146) was expressed in Xenopus oocytes, and currents were recorded using two-microelectrode voltage clamp. Acidosis increased fKv1.4 Delta2-146 C-type inactivation. Replacement of a pore histidine with cysteine (H508C) abolished the increase. Application of positively charged thiol-specific methanethiosulfonate to fKv1.4 Delta2-146 H508C increased C-type inactivation, mimicking the effect of acidosis. Replacement of a pore lysine with cysteine (K532C) abolished the acidosis-induced increase of C-type inactivation. A model of the Kv1.4 pore, based on the crystal structure of KcsA, shows that H508 and K532 lie close together. It is suggested that the acidosis-induced increase of C-type inactivation involves the charge on H508 and K532.

引用

页码：C1114 / C1121

页数：8

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