Contribution of I Ks to ventricular repolarization in canine myocytes.
The role of the slow delayed rectifier K(+) current (I (Ks)) in cardiac repolarization seems to be largely influenced by the experimental conditions including the species and tissue studied. The aim of this study was to determine the contribution of I (Ks) to repolarization in canine ventricular myocytes by measuring the frequency dependent action potential lengthening effect of 10 microM chromanol 293B using sharp microelectrodes. Pretreatment with isoproterenol (2 nM), E-4031 (1 microM), and injection of inward current pulses were applied to modify action potential configuration. Chromanol alone caused moderate but statistically significant lengthening of action potentials at cycle lengths longer than 500 ms. The lengthening effect of chromanol, which was strongly enhanced in the presence of either isoproterenol or E-4031, was proportional to the amplitude of plateau, whereas poor correlation was found with action potential duration. Similar results were obtained when action potential configuration was modified by injection of depolarizing current pulses. Computer simulations revealed that activation of I (Ks) is a sharp function of the plateau amplitude within the physiological range, while elongation of repolarization may enhance I (Ks) only when it is excessive. It was concluded that the effect of I (Ks) on ventricular repolarization critically depends on the level of action potential plateau; however, other factors, like action potential duration, cycle length, or suppression of other K(+) currents can also influence its contribution.
Department of Physiology, University of Debrecen, P.O. Box 22, Debrecen 4012, Hungary.
Balázs
B
Horváth
János
J
Magyar
Norbert
N
Szentandrássy
Péter
P
Birinyi
Péter P
PP
Nánási
Tamás
T
Bányász
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D016764:Cell Polarity / Q000187:drug effects / Q000502:physiology*; D002839:Chromans / Q000494:pharmacology; D003198:Computer Simulation; D051668:Delayed Rectifier Potassium Channels / Q000187:drug effects / Q000502:physiology*; D004285:Dogs; D005260:Female; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006352:Heart Ventricles / Q000187:drug effects; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology*; D010880:Piperidines / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024661:Potassium Channels, Inwardly Rectifying / Q000187:drug effects / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology; D016276:Ventricular Function
D000318:Adrenergic beta-Agonists; D002839:Chromans; D051668:Delayed Rectifier Potassium Channels; D010880:Piperidines; D026902:Potassium Channel Blockers; D024661:Potassium Channels, Inwardly Rectifying; D011725:Pyridines; D013449:Sulfonamides; C063968:E 4031; C103474:6-cyano-4-(N-ethylsulfonyl-N-methylamino)-3-hydroxy-2,2-dimethylchromane; D007545:Isoproterenol