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

Isolated bovine ventricular myocytes were investigated with a two-microelectrode voltage clamp technique. The clamp currents were analyzed in terms of ICa and IK. Possible effects on INa were avoided by superfusing the cells with a Na-free medium. Imipramine (IMI) was applied at a concentration of 3.6 microM. Within the initial 3 min (early phase), IMI reduced peak ICa by 38 +/- 9% but IMI did not change the time constants of inactivation, the voltage dependence of peak ICa 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 ICa. The inward rectifying potassium current (IK1) 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 ICa 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.