PubMed 21044565

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: A , Kv1.2

Title: 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, Werner Treptow, Michael L Klein, Mounir Tarek

Journal, date & volume: Biophys. J., 2010 Nov 3 , 99, L72-4

PubMed link:

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.