Referenced in: none

Automatically associated channels: Kir2.1

Title: Mechanism for attenuated outward conductance induced by mutations in the cytoplasmic pore of Kir2.1 channels.

Authors: Hsueh-Kai Chang, Masayuki Iwamoto, Shigetoshi Oiki, Ru-Chi Shieh

Journal, date & volume: Sci Rep, 2015 , 5, 18404

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/26678093

Abstract
Outward currents through Kir2.1 channels regulate the electrical properties of excitable cells. These currents are subject to voltage-dependent attenuation by the binding of polyamines to high- and low-affinity sites, which leads to inward rectification, thereby controlling cell excitability. To examine the effects of positive charges at the low-affinity site in the cytoplasmic pore on inward rectification, we studied a mutant Kir channel (E224K/H226E) and measured single-channel currents and streaming potentials (Vstream), the latter provide the ratio of water to ions queued in a single-file permeation process in the selectivity filter. The water-ion coupling ratio was near one at a high K(+) concentration ([K(+)]) for the wild-type channel and increased substantially as [K(+)] decreased. On the other hand, fewer ions occupied the selectivity filter in the mutant at all [K(+)]. A model for the Kir channel involving a K(+) binding site in the wide pore was introduced. Model analyses revealed that the rate constants associated with the binding and release to and from the wide-pore K(+) binding site was modified in the mutant. These effects lead to the reduced contribution of a conventional two-ion permeation mode to total conductance, especially at positive potentials, thereby inward rectification.