Purpose: Adenosine triphosphate (ATP)-sensitive K+ (KATP) 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 KATP channels in differentiated hippocampal neuron-derived H19-7 cells.
Methods: The inside-out configuration of the patch-clamp technique was used to investigate KATP channel activities in H19-7 cells in the presence of PGB. Effects of various compounds known to alter KATP channel activities were compared.
Results: The activity of KATP 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 KATP channels reported in pancreatic beta cells. 2,4-Dinitrophenol activated channel activity, but the further addition of glucose (20 mM) or glibenclamide (30 microM) could offset these increments. PGB significantly opened these KATP channel activities in a concentration-dependent fashion with a median effective concentration (EC50) value of 18 microM. A significant increase was noted in the mean open lifetime of KATP 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 KATP channels could be one of the underlying mechanisms of PGB in the reduction of neuronal excitability.