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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.

Original publication

DOI

10.1016/j.nmd.2007.07.009

Type

Journal article

Journal

Neuromuscul Disord

Publication Date

01/2008

Volume

18

Pages

74 - 80

Keywords

Animals, Cromakalim, Diazoxide, Hypokalemic Periodic Paralysis, KATP Channels, Male, Membrane Potentials, Muscle, Skeletal, Patch-Clamp Techniques, Potassium Channel Blockers, Potassium Channels, Inwardly Rectifying, Potassium Deficiency, Rats, Rats, Wistar, Sarcolemma, Vasodilator Agents