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

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

We investigated on the mechanism responsible for the reduced ATP-sensitive K+(KATP) channel activity recorded from skeletal muscle of K+-depleted rats. Patch-clamp and gene expression measurements of KATP channel subunits were performed. A down-regulation of the KATP 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 KATP channel currents of -69.5% in K+-depleted rats was observed. The Kir6.2/SUR2A-B agonist cromakalim showed similar potency in activating the KATP channels of normokalaemic and K+-depleted rats but reduced efficacy in K+-depleted rats. The Kir6.2/SUR1-2B agonist diazoxide activated KATP channels in normokalaemic and K+-depleted rats with equal potency and efficacy. The down-regulation of the Kir6.2 explains the reduced KATP 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 languageEnglish (US)
Pages (from-to)74-80
Number of pages7
JournalNeuromuscular Disorders
Volume18
Issue number1
DOIs
StatePublished - Jan 2008

Keywords

  • Gene expression
  • Hypokalaemic periodic paralysis
  • K channel
  • Skeletal muscle

ASJC Scopus subject areas

  • Clinical Neurology
  • Pediatrics, Perinatology, and Child Health
  • Developmental Neuroscience
  • Neurology

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