ATP sensitivity of the ATP-sensitive K+ channel in intact and permeabilized pancreatic β-cells

Andrei I. Tarasov, Christophe A.J. Girard, Frances M. Ashcroft

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

ATP-sensitive K+ channels (KATP channels) couple cell metabolism to electrical activity and thereby to physiological processes such as hormone secretion, muscle contraction, and neuronal activity. However, the mechanism by which metabolism regulates KATP channel activity, and the channel sensitivity to inhibition by ATP in its native environment, remain controversial. Here, we used {alpha}-toxin to permeabilize single pancreatic β-cells and measure KATP channel ATP sensitivity. We show that the channel ATP sensitivity is approximately sevenfold lower in the permeabilized cell than in the inside-out patch and that this is caused by interaction of Mg-nucleotides with the nucleotide-binding domains of the SUR1 subunit of the channel. The ATP sensitivity observed in permeabilized cells accounts quantitatively for KATP channel activity in intact cells. Thus, our results show that the principal metabolic regulators of K ATP channel activity are MgATP and MgADP.

Original languageEnglish
Pages (from-to)2446-2454
Number of pages9
JournalDiabetes
Volume55
Issue number9
DOIs
Publication statusPublished - 1 Sep 2006

    Fingerprint

Keywords

  • [ATP]
  • [ATP], submembrane ATP concentration
  • Intracellular concentration of ATP
  • K channel, ATP-sensitive K channel
  • LC-CoA, long-chain acyl-CoA
  • NBD, nucleotide-binding domain

Cite this