Abstract
Flupirtine (Flu), a triaminopyridine derivative, is a centrally acting, non-opiate analgesic agent. In this study, effects of Flu on K(+) currents were explored in two types of motor neuron-like cells. Cell exposure to Flu decreased the amplitude of delayed rectifier K(+) current (I(K(DR))) with a concomitant raise in current inactivation in NSC-34 neuronal cells. The dissociation constant for Flu-mediated increase of I(K(DR)) inactivation rate was about 9.8 μM. Neither linopirdine (10 μM), NMDA (30 μM), nor gabazine (10 μM) reversed Flu-induced changes in I(K(DR)) inactivation. Addition of Flu shifted the inactivation curve of I(K(DR)) to a hyperpolarized potential. Cumulative inactivation for I(K(DR)) was elevated in the presence of this compound. Flu increased the amplitude of M-type K(+) current (I(K(M))) and produced a leftward shift in the activation curve of I(K(M)). In another neuronal cells (NG108-15), Flu reduced I(K(DR)) amplitude and enhanced the inactivation rate of I(K(DR)). The results suggest that Flu acts as an open-channel blocker of delayed-rectifier K(+) channels in motor neurons. Flu-induced block of I(K(DR)) is unlinked to binding to NMDA or GABA receptors and the effects of this agent on K(+) channels are not limited to its action on M-type K(+) channels.