Voltage- and rate-dependent depression of Vmax of action potentials by a new antiarrhythmic agent, E-0747, in swine cardiac Purkinje fibers.
Effects of a new antiarrhythmic agent, E-0747, on action potentials of swine cardiac Purkinje fibers were studied using standard microelectrode techniques. E-0747 decreased the maximum rate of rise (Vmax) of action potentials at concentrations higher than 3 X 10(-7) M at a frequency of 1 Hz without change in resting membrane potential. E-0747 (3 X 10(-6) M) shifted the steady-state relationship between the Vmax and the resting membrane potential in a hyperpolarizing direction by 9.2 +/- 0.9 mV. E-0747 depressed the Vmax in a rate-dependent manner. At a concentration of 3 X 10(-6) M, the depression was approximately 50% at a stimulation of 3.3 Hz. E-0747 (3 X 10(-6) M) did not depress the Vmax of the first action potential after a rest period of approximately 30 min, but subsequently reduced the Vmax with successive stimulations reaching a new steady level after approximately 20 min. The time course of recovery from inactivation of the Vmax in the presence of E-0747 (10(-6) M) did not differ from that of the control. E-0747 shortened the action potential duration (APD), but did not affect the ratio of effective refractory period (ERP) to APD. These results suggest that E-0747 depresses the Vmax by closely associating with open and/or inactivated sodium channels. It may be classified as an antiarrhythmic agent of class 1C type of the Vaughan Williams' classification.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D004558:Electric Stimulation; D006329:Heart Conduction System / Q000187:drug effects*; D007473:Ion Channels / Q000378:metabolism; D007700:Kinetics; D008839:Microelectrodes; D010880:Piperidines / Q000494:pharmacology*; D011690:Purkinje Fibers / Q000187:drug effects*; D012964:Sodium / Q000378:metabolism; D013552:Swine; D013997:Time Factors
D000889:Anti-Arrhythmia Agents; D007473:Ion Channels; D010880:Piperidines; C051825:E 0747; D012964:Sodium