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Trends Pharmacol Sci. 2014 Sep;35(9):461-9. doi: 10.1016/j.tips.2014.06.002. Epub 2014 Jul 9.

Altered and dynamic ion selectivity of K+ channels in cell development and excitability.

Author information

1
Department of Biological Sciences, University at Albany, State University of New York, Albany, NY 12222, USA. Electronic address: hchen01@albany.edu.
2
Institut de Pharmacologie Moléculaire et Cellulaire, LabEx Ion Channel Science and Therapeutics, Centre National de la Recherche Scientifique, and Université de Nice Sophia Antipolis, 660 Route des Lucioles, 06560 Valbonne, France.
3
Institut de Pharmacologie Moléculaire et Cellulaire, LabEx Ion Channel Science and Therapeutics, Centre National de la Recherche Scientifique, and Université de Nice Sophia Antipolis, 660 Route des Lucioles, 06560 Valbonne, France. Electronic address: lesage@ipmc.cnrs.fr.

Abstract

K(+) channels play a key role in regulating cellular excitability. It was thought that the strong K(+) selectivity of these channels was static, only altered by mutations in their selectivity filter, which can cause severe genetic disorders. Recent studies demonstrate that selectivity of K(+) channels can also exhibit dynamic changes. Under acidic conditions or in low extracellular K(+) concentrations, the two-pore domain K(+) channel (K2P) TWIK1 becomes permeable to Na(+), shifting from an inhibitory role to an excitatory role. This phenomenon is responsible for the paradoxical depolarization of human cardiomyocytes in pathological hypokalemia, and therefore may contribute to cardiac arrhythmias. In other cell types, TWIK1 produces depolarizing leak currents under physiological conditions. Dynamic ion selectivity also occurs in other K2P channels. Here we review evidence that dynamic selectivity of K2P channels constitutes a new regulatory mechanism of cellular excitability, whose significance is only now becoming appreciated.

KEYWORDS:

K(2P) channels; cationic channels; channelopathies; dynamic ion selectivity; excitability; hypokalemia; ionic pore; pH-sensitive; resting potential

PMID:
25023607
PMCID:
PMC4467785
DOI:
10.1016/j.tips.2014.06.002
[Indexed for MEDLINE]
Free PMC Article

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