Duloxetine blocks cloned Kv4.3 potassium channels

摘要: The effects of duloxetine were examined on cloned Kv4.3 channels stably expressed in CHO cells using the whole-cell patch-clamp technique. Duloxetine decreased peak amplitude currents with an acceleration decay rate current inactivation a concentration-dependent manner. IC(50) values required for blocking and integral 8.4 2.1μM, respectively. accelerated thereby time-to-peak Analysis time dependence drug block produced estimates 21.9μM(-1)s(-1) 165.9s(-1), respective association (k(+1)) dissociation (k(-1)) constants. K(d) value (k(-1)/k(+1)) yielded 7.5μM, which approximates experimental obtained from concentration-response curve. by was voltage-dependent at membrane potential coinciding activation channels. At more positive potential, however, relieved. hyperpolarizing shift voltage steady-state Kv4.3, closed-state subthreshold range. induced significant use-dependent frequencies 1 2Hz. In presence duloxetine, recovery slower than under control conditions. These results demonstrate that exerts binding to open inactivated states these actions may contribute its analgesic effect neuropathic pain.