Electrophysiological effects of desipramine on guinea pig papillary muscles.

The effects of desipramine (DMI) in concentrations between 1 x 10(-7) M and 1 x 10(-4) M on various electrophysiological parameters were evaluated in ventricular papillary muscles of guinea pig. At concentrations less than 5 x 10(-5) M, DMI produced a significant shortening in the action potential duration (APD) measured at both 50% and 100% of repolarization. At 1 x 10(-4) M, the terminal portion of repolarization was so prolonged that the total APD was not significantly different from control values. DMI (greater than 1 X 10(-5) M) did not change the resting potential but significantly, decreased the overshoot potential, the amplitude, and the maximum rate of rise of phase O depolarization (Vmax) and shifted the membrane responsiveness and membrane reactivation curves downward and to the right. The effective refractory period (ERP) was shortened or lengthened, the effect being dependent on the concentration, but always made the ERP long relative to APD. DMI, (1 X 10(-5) M and 5 x 10(-5) M), attenuated and abolished the spontaneous activity and the Ca-mediated action potentials induced in ventricular muscle fibers. The mechanisms responsible for DMI's in vivo arrhythmogenic or antiarrhythmic effects are discussed. In terms of changes in ion conductance most effects can be explained by a reduction in sodium and calcium conductance.