Effects of 4-aminopyridine on rate-related depression of cardiac action potentials.
Canine cardiac Purkinje fibers and atrial trabeculae and rat and cat papillary muscles superfused with a hyperkalemic, hypoxic, and acidotic Tyrode solution were depolarized to membrane potentials (-70 to -60 mV) at which action potential amplitude declined as the coupling intervals of pacing stimuli were prolonged from 500 to 4,500 ms. The rate-related decline of action potential amplitude appeared to be due to time-dependent recovery of the early outward current rather than to a decrease in inward calcium current, since it was prevented by 4-aminopyridine (1.0 mM), but not by isoproterenol (1.0 microM), caffeine (5.0 mM), or CsCl (5-20 mM) and it was accompanied by an exponential increase of developed tension. Experiments using Purkinje fibers mounted in a single sucrose gap chamber demonstrated that the rate-related decline of action potential amplitude was maximal at membrane potentials between -70 and -40 mV and was negligible at less negative or more negative membrane potentials. These results may pertain to the mechanism for deceleration-dependent bundle branch block.
D015761:4-Aminopyridine; D000200:Action Potentials / Q000187:drug effects; D000631:Aminopyridines / Q000494:pharmacology*; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002415:Cats; D002586:Cesium / Q000494:pharmacology; D002712:Chlorides; D004285:Dogs; D005260:Female; D006321:Heart / Q000187:drug effects*; D006325:Heart Atria; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D010210:Papillary Muscles / Q000187:drug effects; D011690:Purkinje Fibers / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D000631:Aminopyridines; D002712:Chlorides; D002586:Cesium; D002110:Caffeine; D015761:4-Aminopyridine; C028019:cesium chloride; D007545:Isoproterenol