Referenced in: none

Automatically associated channels: Kir6.1 , Kir6.2

Title: Differences in the mechanism of metabolic regulation of ATP-sensitive K+ channels containing Kir6.1 and Kir6.2 subunits.

Authors: Tabasum Farzaneh, Andrew Tinker

Journal, date & volume: Cardiovasc. Res., 2008 Sep 1 , 79, 621-31

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/18522960

Abstract
ATP sensitive K(+) channels (K(ATP)) sense adenine nucleotide concentrations and thus couple the metabolic state of the cell to membrane potential. The hetero-octameric complex of a sulphonylurea receptor (SUR2B) and an inwardly rectifying K(+) channel (Kir6.1) and the corresponding native channel in smooth muscle are relatively insensitive to variations in intracellular ATP. Activation of these channels in blood vessels during hypoxia/ischaemia is thought to be mediated via hormonal regulation such as cellular adenosine release or the release of mediators from the endothelium. In contrast, intracellular ATP prominently inhibits Kir6.2 containing complexes, such as those present in cardiac myocytes. Thus, we investigated differences in the mechanism of metabolic regulation of Kir6.1 and Kir6.2 containing K(ATP) channels.We have heterologously expressed K(ATP) channel subunits in HEK293 and CHO cells and studied their function using (86)Rb efflux and patch clamping. We show that rodent Kir6.1/SUR2B has direct intrinsic metabolic sensitivity independent of any regulation by protein kinase A. In contrast to Kir6.2 containing complexes, this was not endowed by the ATP sensitivity of the pore forming subunit but was instead a property of the SUR2B subunit. Mutagenesis of key residues within the nucleotide-binding domains (NBD) implicated both domains in governing the metabolic sensitivity.Kir6.1\SUR2B has intrinsic sensitivity to metabolism endowed by the likely processing of adenine nucleotides at the NBD of SUR2B.