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.