Format

Send to

Choose Destination
Biophys J. 2010 Nov 3;99(9):L72-4. doi: 10.1016/j.bpj.2010.08.069.

Effect of sensor domain mutations on the properties of voltage-gated ion channels: molecular dynamics studies of the potassium channel Kv1.2.

Author information

1
UMR 7565, Structure et Réactivité des Systèmes Moléculaires Complexes, Centre National de Recherche Scientifique-Nancy University, Nancy cedex, France.

Erratum in

  • Biophys J. 2011 Jan 5;100(1):269.
  • Biophys J. 2010 Dec 1;99(11):3859.

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.

PMID:
21044565
PMCID:
PMC2966007
DOI:
10.1016/j.bpj.2010.08.069
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center