Effect of imipramine on calcium and potassium currents in isolated bovine ventricular myocytes

Abstract

Isolated bovine ventricular myocytes were investigated with a two-microelectrode voltage clamp technique. The clamp currents were analyzed in terms of I Ca and I K. Possible effects on I Na were avoided by superfusing the cells with a Na-free medium. Imipramine (IMI) was applied at a concentration of 3.6μM. Within the initial 3 min (early phase), IMI reduced peak I Ca by 38±9% but IMI did not change the time constants of inactivation, the voltage dependence of peak I Ca or its reversal potential. Therefore, we conclude that IMI reduced calcium conductance. After 10 min of exposure (late phase), IMI can also reduce the reversal potential of I Ca. The inward rectifying potassium current (I K1) was transiently enhanced by 15±8% but later (8–10 min) reduced by 19±4%. Washout of IMI completely reversed all the effects within 10 min. Reduction of I Ca diminished the rate of rise and the overshoot of the slow action potential and can explain the shortening of the AP seen in both Na-free and Na-containing media. Possible clinical implications are discussed.