Action of nicorandil on ATP‐sensitive K+ channel in guinea‐pig ventricular myocytes

Keiko Nakayama, Zheng Fan, Fumiaki Marumo, Tohru Sawanobori, Masayasu Hiraoka

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28 Citations (Scopus)

Abstract

Patch‐clamp techniques were used to study the effects of nicorandil (2‐nicotinamiodethyl nitrate) on the adenosine 5′‐triphosphate (ATP)‐sensitive K+ channel current (IK.ATP) in guinea‐pig ventricular myocytes. Nicorandil activated the time‐independent outward current. This effect was dependent on intracellular ATP concentration ([ATP]i) showing a larger effect at 2 mm than at 10 mm [ATP]i The nicorandil‐induced outward current was inhibited by application of 0.3 μm glibenclamide. In the inside‐out patch configuration, 0.3–1.0 mm nicorandil increased the open‐state probability of IK.ATP without a change in its conductance value (about 90pS). This effect was inhibited by glibenclamide. Analysis of the open and closed time distributions showed that nicorandil had no effect on open and closed distributions shorter than 5 ms. On the other hand, nicorandil increased the life time of bursts and decreased the interburst intervals. The inward rectifier K+ channel current was not influenced by internal application of nicorandil. Therefore, we conclude that IK.ATP is the only K+ current activated by nicorandil, and the main effect of nicorandil is on the kinetics of the IK.ATP bursting behaviour. These actions are similar to that of pinacidil on this preparation. 1991 British Pharmacological Society

Original languageEnglish
Pages (from-to)1641-1648
Number of pages8
JournalBritish Journal of Pharmacology
Volume103
Issue number3
DOIs
Publication statusPublished - 1991 Jul
Externally publishedYes

Keywords

  • ATP‐sensitive K channel
  • Nicorandil
  • guinea‐pig ventricular myocytes

ASJC Scopus subject areas

  • Pharmacology

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