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

Neuromuscul Disord. 2008 Jan;18(1):74-80. doi: 10.1016/j.nmd.2007.07.009. Epub 2007 Sep 6.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cromakalim / pharmacology
  • Diazoxide / pharmacology
  • Hypokalemic Periodic Paralysis / genetics
  • Hypokalemic Periodic Paralysis / metabolism
  • Hypokalemic Periodic Paralysis / physiopathology
  • KATP Channels / deficiency*
  • KATP Channels / drug effects
  • KATP Channels / genetics
  • Male
  • Membrane Potentials / drug effects
  • Membrane Potentials / genetics
  • Muscle, Skeletal / metabolism*
  • Muscle, Skeletal / physiopathology
  • Patch-Clamp Techniques
  • Potassium Channel Blockers / pharmacology
  • Potassium Channels, Inwardly Rectifying / drug effects
  • Potassium Channels, Inwardly Rectifying / genetics
  • Potassium Channels, Inwardly Rectifying / metabolism*
  • Potassium Deficiency / genetics
  • Potassium Deficiency / metabolism*
  • Potassium Deficiency / physiopathology
  • Rats
  • Rats, Wistar
  • Sarcolemma / drug effects
  • Sarcolemma / genetics
  • Sarcolemma / metabolism
  • Vasodilator Agents / pharmacology


  • KATP Channels
  • Kir6.2 channel
  • Potassium Channel Blockers
  • Potassium Channels, Inwardly Rectifying
  • Vasodilator Agents
  • Cromakalim
  • Diazoxide