Cardiac ATP-sensitive K+ channel: A target for diadenosine 5′,5″-P1,P5-pentaphosphate

Aleksandar Jovanovic, Alexey E. Alekseev, Andre Terzic

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

In numerous studies the intracellular mononucleotide-dependent gating of ATP-sensitive K+ (KATP) channels has been demonstrated. However, it is not known whether dinucleotide polyphosphates, a family of endogenous compounds structurally-related to ATP, could also modulate this ion conductance. Therefore, in the present study we assessed the direct effect of diadenosine 5′,5″-P1,P5-pentaphosphate (Ap5A) on cardiac KATP channel activity using the inside-out configuration of the patch-clamp technique. Addition of Ap5A (50 μM) to the internal side of membrane patches, excised from guinea-pig ventricular cells, strongly inhibited KATP channel activity. The estimated NPo (where N is the number of channels in the patch and Po the open probability of each channel) was 4.16 ± 0.50 in the absence and 0.85 ± 0.30 in the presence of Ap5A (50 μM). This effect of Ap5A was partially reversible, and the NP0 was 2.26 ± 0.60 after washout of Ap5A. Exposure of KATP channels to increasing concentrations of Ap5A revealed that the Ap5A-induced inhibition is concentration-dependent with the half-maximal effective concentration of 16 μM (Hill coefficient: 1.6). On the basis of these results, we conclude that Ap5A is a potent antagonist of the KATP channel activity. This represents a previously unrecognized property of Ap5A, as well as the discovery of a potentially novel endogenous ligand of myocardial KATP channels.

Original languageEnglish (US)
Pages (from-to)241-244
Number of pages4
JournalNaunyn-Schmiedeberg's Archives of Pharmacology
Volume353
Issue number2
DOIs
StatePublished - Jan 1 1996

Keywords

  • ATP-sensitive K channel
  • Cardiomyocyte
  • Channel gating
  • Diadenosine pentaphosphate
  • Diadenosine polyphosphates
  • Heart

ASJC Scopus subject areas

  • Pharmacology

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