Article

Helical motion of an S4 voltage sensor revealed by gating pore currents.

Department of Pharmacology, University of Washington, Seattle, USA.
Channels (Austin, Tex.) (Impact Factor: 2.32). 03/2010; 4(2):75-7. DOI: 10.4161/chan.4.2.10998
Source: PubMed

ABSTRACT The mechanism by which the voltage sensors of voltage-gated ion channels move gating charge during the activation process is a subject of active debate. In this issue of Channels, Gamal El-Din et al. probe the movements of the S4 voltage sensor of Shaker K(+) channels through clever use of omega gating pore currents generated by paired gating-charge mutations. Their results provide strong support for a sliding helix or helical screw mechanism of gating charge movement.

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    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.
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