The opening effect of pregabalin on ATP-sensitive potassium channels in differentiated hippocampal neuron-derived H19-7 cells

Purpose: Adenosine triphosphate (ATP)-sensitive K⁺ (K _ATP) channels can couple an intracellular metabolic state to an electrical activity, which is important in the control of neuronal excitability and seizure propagation. We investigated whether the newer antiepileptic drug, pregabalin (PGB), could exert effects on K_ATP channels in differentiated hippocampal neuron-derived H19-7 cells. Methods: The inside-out configuration of the patch-clamp technique was used to investigate K _ATP channel activities in H19-7 cells in the presence of PGB. Effects of various compounds known to alter K_ATP channel activities were compared. Results: The activity of K_ATP channels in these cells was characterized. The single-channel conductance from a linear current-voltage relation was 78 ± 2 pS (n = 8) with a reversal potential of 63 ± 2 mV (n = 8), similar to that of K_ATP channels reported in pancreatic β cells. 2,4-Dinitrophenol activated channel activity, but the further addition of glucose (20 mM) or glibenclamide (30 μM) could offset these increments. PGB significantly opened these K_ATP channel activities in a concentration-dependent fashion with a median effective concentration (EC₅₀) value of 18 μM. A significant increase was noted in the mean open lifetime of K_ATP channels in the presence of PGB (1.71 ± 0.04 to 5.62 ± 0.04 ms). Conclusions: This study suggests that in differentiated hippocampal neuron-derived H19-7 cells, the opening effect on K_ATP channels could be one of the underlying mechanisms of PGB in the reduction of neuronal excitability.