Mechanism of increased amplitude and duration of the plateau with sudden shortening of diastolic intervals in rabbit ventricular cells.
Action potentials and membrane currents were recorded from isolated single ventricular cells from rabbit hearts using the suction pipette whole-cell clamp method. Action potentials elicited after short diastolic intervals of less than 2 seconds showed an increase and prolongation of the plateau compared to those elicited after a 10-second rest period. The recovery of the tetrodotoxin-insensitive secondary inward current revealed a transient increase at short diastolic intervals above the level of full recovery (after 10 seconds). The increased secondary inward current recovery, however, was voltage-dependent, and the period of its increase did not cover the entire diastolic intervals of the action potential overshoots, suggesting the contribution of another ionic current to the changes in potential. During depolarizing voltage steps, from + to -20 mV, a rapid activating and then inactivating outward current was elicited, which overlapped the calcium current. This outward current exhibited time- and voltage-dependent properties similar to those of the transient outward current in Purkinje and other cardiac preparations. The recovery of the transient outward current was slow, achieving only 75% of its full level at 2 seconds, whereas the same level of calcium current recovery was achieved at 200 milliseconds. The application of 4-aminopyridine suppressed most of the transient outward current, and the rest of the current was abolished by caffeine or Co2+. The 4-aminopyridine sensitive transient outward current exhibited slow recovery kinetics compared to those of the other or calcium current, and its inhibition caused elimination of the augmented plateau during electrical restitution. The application of verapamil or Co2+ for inhibition of secondary inward current also abolished the action potential overshoot. These results indicate that an increase and prolongation of the plateau at short diastolic intervals are produced by the slower recovery from inactivation in the 4-aminopyridine-sensitive transient outward current than that in the calcium current.
D015761:4-Aminopyridine; D000200:Action Potentials / Q000187:drug effects; D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D004553:Electric Conductivity; D006168:Guinea Pigs; D006339:Heart Rate; D006352:Heart Ventricles / Q000166:cytology; D066298:In Vitro Techniques; D007473:Ion Channels / Q000502:physiology; D008564:Membrane Potentials; D009200:Myocardial Contraction; D011817:Rabbits; D013997:Time Factors; D016276:Ventricular Function
D000631:Aminopyridines; D007473:Ion Channels; D002110:Caffeine; D015761:4-Aminopyridine