Drug-induced changes in action potential duration are proportional to action potential duration in rat ventricular myocardium

László Bárándi, Gábor Harmati, Balázs Horváth, Norbert Szentandrássy, János Magyar, András Varró, Péter P. Nánási, Tamás Bányász

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Several cardioactive agents exhibit direct or reverse rate-dependent effects on action potential duration (APD) depending on the experimental conditions. Recently, a new theory has been proposed, suggesting that the reverse rate-dependent mode of drug-action may be a common property of canine, rabbit, guinea pig and human cardiac tissues, and this phenomenon is based on the dependence of drug-action on baseline APD. The aim of the present work was to examine the limitations of this hypothesis by studying the APD lengthening effect of K+ channel blockers and the APD shortening effect of Ca2+ channel blockers during the electrical restitution process of rat ventricular action potentials. Rat ventricular muscle was chosen because it has a set of ion currents markedly different from those of other species, its APD is shorter by one order of magnitude than that of the "plateau- forming" larger mammals, and most importantly, its APD increases at higher heart rates - opposite to many other species. The restitution of APD was studied as a function of the diastolic interval, a parameter indicating the proximity of action potentials. It was found that drug-induced APD changes in rat myocardium are proportional with the pre-drug value of APD but not with the diastolic interval, indicating that not the proximity of consecutive action potentials, but the baseline APD itself may determine the magnitude of drug-induced APD changes.

Original languageEnglish
Pages (from-to)309-313
Number of pages5
JournalGeneral physiology and biophysics
Volume29
Issue number3
DOIs
Publication statusPublished - Sep 1 2010

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Keywords

  • Action potential duration
  • Electrical restitution
  • Membrane current
  • Reverse rate dependence
  • Ventricular repolarization

ASJC Scopus subject areas

  • Biophysics
  • Physiology

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