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Effect of Sensor Domain Mutations on the Properties of Voltage-Gated Ion Channels: Molecular Dynamics Studies of the Potassium Channel Kv1.2

Authors :
Lucie Delemotte
Michael L. Klein
Werner Treptow
Mounir Tarek
Source :
Biophysical Journal. 99(9):L72-L74
Publication Year :
2010
Publisher :
Elsevier BV, 2010.

Abstract

The effects on the structural and functional properties of the Kv1.2 voltage-gated ion channel, caused by selective mutation of voltage sensor domain residues, have been investigated using classical molecular dynamics simulations. Following experiments that have identified mutations of voltage-gated ion channels involved in state-dependent omega currents, we observe for both the open and closed conformations of the Kv1.2 that specific mutations of S4 gating-charge residues destabilize the electrostatic network between helices of the voltage sensor domain, resulting in the formation of hydrophilic pathways linking the intra- and extracellular media. When such mutant channels are subject to transmembrane potentials, they conduct cations via these so-called “omega pores.” This study provides therefore further insight into the molecular mechanisms that lead to omega currents, which have been linked to certain channelopathies.

Details

ISSN :
00063495
Volume :
99
Issue :
9
Database :
OpenAIRE
Journal :
Biophysical Journal
Accession number :
edsair.doi.dedup.....0e39877a768e1f9c0ad0a35748a561c0
Full Text :
https://doi.org/10.1016/j.bpj.2010.08.069