Figure 5.

Comparison of the effects of flupirtine on K_V7 channels in hippocampal, DRG and dorsal horn neurons. Cultured hippocampal (HC), DRG or dorsal horn (DH) neurons were clamped at −30 mV and hyperpolarized to −55 mV for 1 s periods every 10 s in order to de-activate K_V7 channels. Drugs were present for at least 8 s before their effects on the currents were determined. (A) Representative traces measured in a DRG neuron in the presence of solvent, 30 µM flupirtine or 30 µM linopirdine. The shift in the outward current at −30 mV is indicated by the arrows. (B) Normalized amplitudes of outward currents at −30 mV were measured in the presence of solvent or 30 µM linopirdine in hippocampal (n = 5), DRG (n = 6) and dorsal horn (n = 4) neurons. (C) Normalized amplitudes of currents measured at −30 mV in the absence and presence of increasing concentrations of flupirtine were determined in hippocampal (n = 9), DRG (n = 10) and dorsal horn (n = 8) neurons, respectively. EC₅₀ values were 6.1, 4.4 and 5.4 µM in hippocampal, DRG and dorsal horn neurons, respectively. The maximal effects observed in hippocampal neurons were significantly different from those in DRG or dorsal horn neurons at P < 0.01.