Referenced in: none

Automatically associated channels: Kir6.2

Title: Inward rectification in KATP channels: a pH switch in the pore.

Authors: T Baukrowitz, S J Tucker, U Schulte, K Benndorf, J P Ruppersberg, B Fakler

Journal, date & volume: EMBO J., 1999 Feb 15 , 18, 847-53

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/10022827

Abstract
Inward-rectifier potassium channels (Kir channels) stabilize the resting membrane potential and set a threshold for excitation in many types of cell. This function arises from voltage-dependent rectification of these channels due to blockage by intracellular polyamines. In all Kir channels studied to date, the voltage-dependence of rectification is either strong or weak. Here we show that in cardiac as well as in cloned KATP channels (Kir6.2 + sulfonylurea receptor) polyamine-mediated rectification is not fixed but changes with intracellular pH in the physiological range: inward-rectification is prominent at basic pH, while at acidic pH rectification is very weak. The pH-dependence of polyamine block is specific for KATP as shown in experiments with other Kir channels. Systematic mutagenesis revealed a titratable C-terminal histidine residue (H216) in Kir6.2 to be the structural determinant, and electrostatic interaction between this residue and polyamines was shown to be the molecular mechanism underlying pH-dependent rectification. This pH-dependent block of KATP channels may represent a novel and direct link between excitation and intracellular pH.