Characterization of riluzole-induced stimulation of large-conductance calcium-activated potassium channels in rat pituitary GH(3) cells

Background: Riluzole is known to be an inhibitor of glutamatergic neurotran smission, Transmitter release from nerve terminals can be regulated by the activity of large-conductance Ca2+-activated K+ (BKCa) channels, Methods: T he ionic mechanism of actions of riluzole was investigated in neuroendocrin e (GH(3) and PC12 cells), using the whole-cell patch-clamp and inside-out e xcised patch configurations. Results: In GH(3) cells, riluzole at 0.3-100 mu moy/L increased the amplitu de of Ca2+-activated K+ current (IK(Ca)) in a concentration-dependent manne r with a half maximal concentration of 5 mu mol/L. The riluzole-induced inc rease in outward current was not be suppressed by glibenclamide (10 umol/L) or apamin (200 nmol/L). However, iberiotoxin (200 nmol/L) or tetrandrine ( 10 mu mol/L) can effectively suppress riluzole-induced I-K(Ca). Under insid e-out patch recording mode, riluzole (10 mu mol/L) applied intracellularly can increase the opening probability of large-conductance Ca2+- activated K + (BKCa channels, but did not affect their single-channel conductance. The riluzole-induced change in the kinetic behavior of BKCa channels is due to an increase in mean open time and a decrease in mean closed time. Riluzole caused a left shift in the midpoint for voltage-dependent opening. Riluzole stimulated activity of BKCa is independent on internal Ca2+, Riluzole (30 mu mol/L) did not affect the amplitude of voltage-dependent K+ current, but it produced a slight reduction of L-type voltage-dependent Ca2+ current. U nder current clamp mode, riluzole (10 mu mol/L) decreased the firing rate o f action potentials induced by thyrotropin releasing hormone (10 umol/L) in GH(3) cells. In rat pheochromocytoma PC12 cells, riluzole also increased t he activity of BKCa channels without altering their channel conductance. Conclusion: This study shows that riluzole can stimulate the activity of BK Ca channel in neuroendocrine cells.