Imipramine blocks the transient outward potassium current in rat ventricular myocytes
Abstract
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.
Keywords:
(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.