Electrophysiologic Effects Of Cardiomyopeptidin On Ventricular Myocytes Of Guinea Pigs And Rats

Objectives: To determine the effects of cardiomyopeptidin on L-type calcium channels, sodium channels and potassium channels in ventricular myocytes of guinea pigs and rats. To study the pharmacological mechanism of cardiomyopeptidin on the ion channels of myocardium.Methods: Single ventricular myocytes of guinea pigs and rats were obtained by enzymatic dissociation method. The influence of a broad spectrum dosages of cardiomyopeptidin on L-type calcium current (I_Ca-L), sodium current (I_Na), inward rectifier current (I_K1) and transient outward potassium current (I_to) of guinea pigs or rats was recorded by the technique of whole-cell patch clamp.Results: The action potential and ion currents could be recorded in the isolated ventricular myocytes of guinea pigs and rats, which indicated the myocytes had satisfactory electrophysiological properties.At the test potential of +10 mV, cardiomyopeptidin(l, 5, 10, 50, 100 and 500 mg/L) increased L-type calcium current in a dose-dependent manner, the increasing rate were (5±4)%, (21±5)%, (30±5)%, (55±8)%, (76±11)% and (88±14)% respectively. The half maximal effect concentration (EC50) was (18±6) mg/L. The time to peak (TTP) was decreased from (6.7 ± 0.9) ms to (5.9 ±0.7) ms (P<0.01) by cardiomyopeptidin (50 mg/L). In the presence of cardiomyopeptidin (50 mg/L), the current density-voltage curve was moved down and active potential, peak potential, and the shape of the curve had no changes. The activation curve was moved to more negative potential, the half active potential (V_0.5) was (-4.3±0.4) mV and (-8.6±0.4) mV (P<0.05) in control and cardiomyopeptidin (50 mg/L) respectively. The steady inactivation curve and the steady inactivation recovery curve were not affected.At the test potential of -20 mV, cardiomyopeptidin(l, 5, 10, 50, 100 and 500 mg/L) decreased I_Na in a dose-dependent manner, the inhibition rate were (0±1)%, (6+2)%, (10±2)%, (15±1)%, (22±9)% and (30+6)% respectively. The time to peak (TTP) was delayed from (2.8 ± 0.7) ms to (3.0 ± 0.8) ms (P<0.05) by cardiomyopeptidin (50 mg/L). In the presence of cardiomyopeptidin (50 mg/L), the current density-voltage curve of I_Na was shifted and without change of its active...