title: Ion conduction through the hERG potassium channel.
abstract: The inward rectifier voltage-gated potassium channel hERG is of primary importance for the regulation of the membrane potential of cardiomyocytes. Unlike most voltage-gated K(+)-channels, hERG shows a low elementary conductance at physiological voltage and potassium concentration. To investigate the molecular features underlying this unusual behavior, we simulated the ion conduction through the selectivity filter at a fully atomistic level by means of molecular dynamics-based methods, using a homology-derived model. According to our calculations, permeation of potassium ions can occur along two pathways, one involving site vacancies inside the filter (showing an energy barrier of about 6 kcal mol(-1)), and the other characterized by the presence of a knock-on intermediate (about 8 kcal mol(-1)). These barriers are indeed in accordance with a low conductance behavior, and can be explained in terms of a series of distinctive structural features displayed by the hERG ion permeation pathway.
authors.affiliation: Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Ceccarini
authors.forename: Matteo
authors.initials: M
authors.lastname: Masetti
authors.forename: Andrea
authors.initials: A
authors.lastname: Cavalli
authors.forename: Maurizio
authors.initials: M
authors.lastname: Recanatini
mesh_terms: D003198:Computer Simulation; D018360:Crystallography, X-Ray / Q000379:methods; D000072237:ERG1 Potassium Channel; D004553:Electric Conductivity; D004594:Electrophysiology; D051638:Ether-A-Go-Go Potassium Channels / Q000378:metabolism*; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology; D007477:Ions; D008051:Lipid Bilayers / Q000737:chemistry; D008564:Membrane Potentials; D008954:Models, Biological; D008958:Models, Molecular; D008968:Molecular Conformation; D009038:Motion; D011188:Potassium / Q000737:chemistry
chemical_list: D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D007477:Ions; C000606913:KCNH2 protein, human; D008051:Lipid Bilayers; D011188:Potassium