Reversal of the ATP-liganded state of ATP-sensitive K+ channels by adenylate kinase activity

Jose Ruben Elvir-Mairena, Aleksandar Jovanovic, Luis Alberto Gomez, Alexey E. Alekseev, Andre Terzic

Research output: Contribution to journalArticle

53 Scopus citations

Abstract

The mechanism that promotes transition from the ATP- to the ADP-liganded state of ATP-sensitive K+ (K(ATP)) channels and consequent channel opening in a cytosolic environment of high ATP concentration has yet to be understood. A mechanism examined here that could reverse the ATP-inhibited state is based on the action of adenylate kinase to catalyze phosphoryl transfer between ATP and AMP, resulting in transformation of ATP into ADP. In membrane patches excised from guinea pig cardiomyocytes, AMP alone did not affect channel behavior but increased the open probability of ATP-inhibited K(ATP) channels. This required MgCl2 and a hydrolyzable form of ATP and was prevented by P1,P5-di-adenosine-5'-pentaphosphate, an inhibitor of adenylate kinase. The single channel amplitude and kinetics of channel openings induced by the ADP-generating substrates of adenylate kinase, AMP and MgATP, were indistinguishable from the biophysical properties of the K(ATP) channel exhibited after addition of MgADP. In whole cell voltage- clamped cardiomyocytes, introduction of exogenous adenylate kinase along with millimolar MgATP and AMP induced a K+ current that was suppressed by a sulfonylurea blocker of K(ATP) channels. Enriched sarcolemmal membrane preparations were found to possess ATP-AMP phosphotransferase activity with properties attributable to an extramitochondrial isoform of adenylate kinase. These results indicate that adenylate kinase is a naturally occurring component of sarcolemmal membranes that could provide dynamic governance of K(ATP) channel opening through its phosphoryl transfer catalytic action in the microenvironment of the channel.

Original languageEnglish (US)
Pages (from-to)31903-31908
Number of pages6
JournalJournal of Biological Chemistry
Volume271
Issue number50
DOIs
StatePublished - Dec 30 1996

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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