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PLoS One. 2012;7(11):e49017. doi: 10.1371/journal.pone.0049017. Epub 2012 Nov 2.

Ion conduction through the hERG potassium channel.

Author information

1
Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy.

Abstract

The inward rectifier voltage-gated potassium channel hERG is of primary importance for the regulation of the membrane potential of cardiomyocytes. Unlike most voltage-gated K(+)-channels, hERG shows a low elementary conductance at physiological voltage and potassium concentration. To investigate the molecular features underlying this unusual behavior, we simulated the ion conduction through the selectivity filter at a fully atomistic level by means of molecular dynamics-based methods, using a homology-derived model. According to our calculations, permeation of potassium ions can occur along two pathways, one involving site vacancies inside the filter (showing an energy barrier of about 6 kcal mol(-1)), and the other characterized by the presence of a knock-on intermediate (about 8 kcal mol(-1)). These barriers are indeed in accordance with a low conductance behavior, and can be explained in terms of a series of distinctive structural features displayed by the hERG ion permeation pathway.

PMID:
23133669
PMCID:
PMC3487835
DOI:
10.1371/journal.pone.0049017
[Indexed for MEDLINE]
Free PMC Article

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