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Physical determinants of strong voltage sensitivity of K(+) channel block.


ABSTRACT: Strong voltage sensitivity of inward-rectifier K(+) (Kir) channels has been hypothesized to arise primarily from an intracellular blocker displacing up to five K(+) ions from the wide, intracellular part of the ion conduction pore outwardly across the narrow ion-selectivity filter. The validity of this hypothesis depends on two assumptions: (i) that five ion sites are located intracellular to the filter and (ii) that the blocker can force essentially unidirectional K(+) movement in a pore region generally wider than the combined dimensions of the blocker plus a K(+) ion. Here we present a crystal structure of the cytoplasmic portion of a Kir channel with five ions bound and demonstrate that a constriction near the intracellular end of the pore, acting as a gasket, prevents K(+) ions from bypassing the blocker. This heretofore unrecognized 'gasket' ensures that the blocker can effectively displace K(+) ions across the selectivity filter to generate exceedingly strong voltage sensitivity.

SUBMITTER: Xu Y 

PROVIDER: S-EPMC3009588 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

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Physical determinants of strong voltage sensitivity of K(+) channel block.

Xu Yanping Y   Shin Hyeon-Gyu HG   Szép Szilvia S   Lu Zhe Z  

Nature structural & molecular biology 20091115 12


Strong voltage sensitivity of inward-rectifier K(+) (Kir) channels has been hypothesized to arise primarily from an intracellular blocker displacing up to five K(+) ions from the wide, intracellular part of the ion conduction pore outwardly across the narrow ion-selectivity filter. The validity of this hypothesis depends on two assumptions: (i) that five ion sites are located intracellular to the filter and (ii) that the blocker can force essentially unidirectional K(+) movement in a pore region  ...[more]

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