Opening of cardiac sarcolemmal K(ATP) channels by dinitrophenol separate from metabolic inhibition

A. E. Alekseev, L. A. Gomez, L. A. Aleksandrova, P. A. Brady, A. Terzic

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Opening of ATP-sensitive K+ (K(ATP)) channels by the uncoupler of oxidative phosphorylation, 2,4 dinitrophenol (DNP), has been assumed to be secondary to metabolic inhibition and reduced intracellular ATP levels. Herein, we present data which show that DNP (200 μM) can induce opening of cardiac K(ATP) channels, under whole-cell and inside-out conditions, despite millimolar concentrations of ATP (1-2.5 mM). DNP-induced currents had a single channel conductance (71 pS), inward rectification, reversal potential, and intraburst kinetic properties (open time constant, τ(open): 4.8 msec; fast closed time constant, τ(closed(F)): 0.33 msec) characteristic of K(ATP), channels suggesting that DNP did not affect the pore region of the channel, but may have altered the functional coupling of the ATP-dependent channel gating. A DNP analogue, with the pH-titrable hydroxyl replaced by a methyl group, could not open K(ATP) channels. The pH-dependence of the effect of DNP on channel opening under whole-cell, cell-attached, and inside-out conditions suggested that transfer of protonated DNP across the sarcolemma is essential for activation of K(ATP) channels in the presence of ATP. We conclude that the use of DNP for metabolic stress-induced K(ATP) channel opening should be reevaluated.

Original languageEnglish (US)
Pages (from-to)203-214
Number of pages12
JournalJournal of Membrane Biology
Volume157
Issue number2
DOIs
StatePublished - Jun 19 1997

Keywords

  • ATP-sensitive K channels
  • Cardiac
  • DNP
  • Protonophore
  • Uncoupler of oxidative phosphorylation
  • pH

ASJC Scopus subject areas

  • Biophysics
  • Physiology
  • Cell Biology

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