Referenced in: none

Automatically associated channels: Kir2.1 , Kv10.1

Title: Localization of PIP2 activation gate in inward rectifier K+ channels.

Authors: Jun Xiao, Xiao-Guang Zhen, Jian Yang

Journal, date & volume: Nat. Neurosci., 2003 Aug , 6, 811-8

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/12858177

Abstract
Ion channels respond to changes in transmembrane voltage or ligand concentration by opening or closing an activation gate. In voltage-gated K+ channels, this gate has been localized to an intracellular bundle crossing. Here we examined whether this bundle crossing, or the more internal cytoplasmic pore, acts as a gate for PIP2 activation of inward rectifier K+ (Kir) channels expressed in Xenopus laevis oocytes. We studied the open/closed state-dependence of the accessibility of intracellular cationic modifiers to a position (residue Ile176 in the TM2 helix of Kir2.1) more external to the bundle crossing. Cd2+ blocked I176C mutant channels much more weakly in the closed state than in the open state, but Ag+ and sulfhydryl-specific methanethiosulfonate reagents modified the channels with similar rates in both states. These results suggest that the TM2 helices undergo conformation changes upon PIP2 binding/unbinding, but neither they nor the cytoplasmic pore close fully to form a physical gate for K+ conduction.