Referenced in: none

Automatically associated channels: Cav1.1 , Kir6.1 , Kir6.2

Title: Reduced expression of Kir6.2/SUR2A subunits explains KATP deficiency in K+-depleted rats.

Authors: Domenico Tricarico, Antonietta Mele, Birgit Liss, Frances M Ashcroft, Andrew L Lundquist, Reshma R Desai, Alfred L George, Diana Conte Camerino

Journal, date & volume: Neuromuscul. Disord., 2008 Jan , 18, 74-80

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/17825556

Abstract
We investigated on the mechanism responsible for the reduced ATP-sensitive K(+)(K(ATP)) channel activity recorded from skeletal muscle of K(+)-depleted rats. Patch-clamp and gene expression measurements of K(ATP) channel subunits were performed. A down-regulation of the K(ATP) channel subunits Kir6.2(-70%) and SUR2A(-46%) in skeletal muscles of K(+)-depleted rats but no changes in the expression of Kir6.1, SUR1 and SUR2B subunits were observed. A reduced K(ATP) channel currents of -69.5% in K(+)-depleted rats was observed. The Kir6.2/SUR2A-B agonist cromakalim showed similar potency in activating the K(ATP) channels of normokalaemic and K(+)-depleted rats but reduced efficacy in K(+)-depleted rats. The Kir6.2/SUR1-2B agonist diazoxide activated K(ATP) channels in normokalaemic and K(+)-depleted rats with equal potency and efficacy. The down-regulation of the Kir6.2 explains the reduced K(ATP) channel activity in K(+)-depleted rats. The lower expression of SUR2A explains the reduced efficacy of cromakalim; preserved SUR1 expression accounts for the efficacy of diazoxide. Kir6.2/SUR2A deficiency is associated with impaired muscle function in K(+)-depleted rats and in hypoPP.