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Coupling of activation and inactivation gate in a K+-channel: potassium and ligand sensitivity.


ABSTRACT: Potassium (K(+))-channel gating is choreographed by a complex interplay between external stimuli, K(+) concentration and lipidic environment. We combined solid-state NMR and electrophysiological experiments on a chimeric KcsA-Kv1.3 channel to delineate K(+), pH and blocker effects on channel structure and function in a membrane setting. Our data show that pH-induced activation is correlated with protonation of glutamate residues at or near the activation gate. Moreover, K(+) and channel blockers distinctly affect the open probability of both the inactivation gate comprising the selectivity filter of the channel and the activation gate. The results indicate that the two gates are coupled and that effects of the permeant K(+) ion on the inactivation gate modulate activation-gate opening. Our data suggest a mechanism for controlling coordinated and sequential opening and closing of activation and inactivation gates in the K(+)-channel pore.

SUBMITTER: Ader C 

PROVIDER: S-EPMC2750023 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature

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Coupling of activation and inactivation gate in a K+-channel: potassium and ligand sensitivity.

Ader Christian C   Schneider Robert R   Hornig Sönke S   Velisetty Phanindra P   Vardanyan Vitya V   Giller Karin K   Ohmert Iris I   Becker Stefan S   Pongs Olaf O   Baldus Marc M  

The EMBO journal 20090806 18


Potassium (K(+))-channel gating is choreographed by a complex interplay between external stimuli, K(+) concentration and lipidic environment. We combined solid-state NMR and electrophysiological experiments on a chimeric KcsA-Kv1.3 channel to delineate K(+), pH and blocker effects on channel structure and function in a membrane setting. Our data show that pH-induced activation is correlated with protonation of glutamate residues at or near the activation gate. Moreover, K(+) and channel blockers  ...[more]

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