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

Delemotte L, Treptow W, Klein ML, Tarek M

Biophysical Journal 99 (9) L72-L74 [2010-11-00; online 2010-11-00]

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.

Lucie Delemotte

SciLifeLab Fellow

PubMed 21044565

DOI 10.1016/j.bpj.2010.08.069

Crossref 10.1016/j.bpj.2010.08.069

Publications 9.5.0