Further characterization of the effects of imipramine on plateau membrane currents in guinea-pig ventricular myocytes

Abstract

The effects of imipramine, a tricyclic antidepressant, on action potential characteristics and plateau membrane currents were studied in isolated guinea-pig ventricular myocytes, using the whole cell configuration of the patch-clamp technique. Imipramine (1, 5 and 15 mumols/l) decreased in a concentration-dependent manner the amplitude and shortened the duration of the action potential, but it had no effect on resting membrane potential. At all three concentrations tested, imipramine decreased the delayed outward potassium current, this effect being apparently voltage-independent since it did not modify the activation curve. Imipramine, 5 and 15 mumols/l, also produced an inhibition of the peak high threshold calcium current, but did not change the shape of the current-voltage relationship or the apparent reversal potential of this current. Therefore, imipramine probably decreased the maximum available calcium conductance. However, the inward rectifying potassium current was not affected by any concentration of imipramine tested. Imipramine, 1 and 5 mumols/l, shortened the duration of the action potentials elicited in the presence of the inorganic calcium channel blocker cobalt chloride, and at 5, but not at 1 mumol/l, also shortened the action potentials obtained in the presence of the sodium channel blocker tetrodotoxin. Washout of imipramine completely reversed all its effects within 15 minutes. All these results suggest that imipramine at a concentration of 1 mumol/l produced a shortening in action potential duration by inhibiting the late sodium current flowing during the plateau phase of the action potential. At concentrations of 5 and 15 mumols/l the effect of imipramine on action potential duration can also be explained by a blocking effect on the high threshold calcium current.