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

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 t...

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Detalles Bibliográficos
Autores principales: Xu, Yanping, Shin, Hyeon-Gyu, Szép, Szilvia, Lu, Zhe
Formato: Texto
Lenguaje:English
Publicado: 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3009588/
https://www.ncbi.nlm.nih.gov/pubmed/19915587
http://dx.doi.org/10.1038/nsmb.1717
Descripción
Sumario: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.