General Physiology and Biophysics Vol.29, No.3, p.309-313, 2010
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Title: Drug-induced changes in action potential duration are proportional to action potential duration in rat ventricular myocardium |
Author: László Bárándi, Gábor Harmati, Balázs Horváth, Norbert Szentandrássy, János Magyar, András Varró, Péter P. Nánási and Tamás Bányász |
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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.
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Keywords: Action potential duration — Electrical restitution — Membrane current — Reverse rate dependence — Ventricular repolarization |
Year: 2010, Volume: 29, Issue: 3 |
Page From: 309, Page To: 313 |
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doi:10.4149/gpb_2010_03_309
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