Drug-induced changes in action potential duration are proportional to action potential duration in rat ventricular myocardium.
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 Ca(2+) 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.
Bárándi
László
L
Department of Physiology, University of Debrecen, Nagyerdei krt 98, H-4012 Debrecen, Hungary.
Harmati
Gábor
G
Horváth
Balázs
B
Szentandrássy
Norbert
N
Magyar
János
J
Varró
András
A
Nánási
Péter P
PP
Bányász
Tamás
T
D015761:4-Aminopyridine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004285:Dogs; D055724:Electrophysiological Phenomena; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008955:Models, Cardiovascular; D009543:Nifedipine / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D013045:Species Specificity; D019789:Tetraethylammonium / Q000494:pharmacology
D002121:Calcium Channel Blockers; D026902:Potassium Channel Blockers; D019789:Tetraethylammonium; D015761:4-Aminopyridine; D009543:Nifedipine