Aim: To examine the effects of imipramine on transient outward potassium current (I(to) in rat ventricular myocytes.
Methods: The patch-clamp whole-cell recording techniques were used.
Results: Imipramine resulted in a concentration-dependent inhibition of I(to) with the IC50 of 6.0 mumol.L-1 and a concentration-dependent acceleration of I(to) inactivation. The blocking showed no difference at different testing membrane potentials. Imipramine produced slight effects (about 3 and 4 mV, respectively) on steady-state activation and inactivation curves of I(to), and tended to prolong the recovery of I(to) from inactivation (tau control = 37 +/- 11 ms; tau drug = 58 +/- 17 ms), but not significant (n = 4, P > 0.05). The inhibitory effect of imipramine on Ito was increased when the prepulses were prolonged progressively from 0 to 120 ms. (tau control = 22 +/- 8 ms; tau drug = 14 +/- 5 ms).
Conclusions: Imipramine blocked Ito in concentration-dependent but voltage-independent manners, and with "open channel blocking" properties.