Allosteric effects of permeating cations on gating currents during K+ channel deactivation

被引:56
作者
Chen, FSP [1 ]
Steele, D [1 ]
Fedida, D [1 ]
机构
[1] QUEENS UNIV, DEPT PHYSIOL, KINGSTON, ON K7L 3N6, CANADA
关键词
potassium channel; Kv1.5; gating current;
D O I
10.1085/jgp.110.2.87
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
K+ channel gating currents are usually measured ill the absence of permeating ions, when a common feature of channel closing is a rising phase of off-gating current and slow subsequent decay. Current models of gating invoke a concerted rearrangement of subunits just before die open state to explain this very slow charge return from opening potentials. We have measured gating currents from the voltage-gated K+ channel, Kv1.5, highly overexpressed in human embryonic kidney cells. In the presence of permeating K+ or Cs+, we show, by comparison with data obtained in the absence of permeant ions, that there is a rapid return of charge after depolarizations, Measurement of off-gating currents on repolarization before and after K+ dialysis from cells allowed a comparison of off-gating current amplitudes and time course in the same cells. Parallel experiments utilizing the low permeability of Cs+ through Kv1.5 revealed similar rapid charge return during measurements of off-gating currents at E-Cs. Such effects could not be reproduced in a nonconducting mutant (W472F) of Kv1.5, in which, by definition, ion permeation was macroscopically absent. This preservation of a fast kinetic structure of off-gating currents on return from potentials at which channels open suggests an allosteric modulation by permeant cations. This may arise fi om a direct action on a slow step late in the activation pathway, or via a retardation in the rate of C-type inactivation. The activation energy barrier for K+ channel closing is reduced, which may be important during repetitive action potential spiking where ion channels characteristically undergo continuous cyclical activation and deactivation.
引用
收藏
页码:87 / 100
页数:14
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