Abstract
Background
Riluzole is known to be an inhibitor of glutamatergic neurotransmission. Transmitter release from nerve terminals can be regulated by the activity of large-conductance Ca2+-activated K+ (BKCa) channels.
Methods
The ionic mechanism of actions of riluzole was investigated in neuroendocrine (GH3 and PC12 cells), using the whole-cell patch-clamp and inside-out excised patch configurations.
Results
In GH3 cells, riluzole at 0.3-100 µmol/L increased the amplitude of Ca2+ -activated K+ current (IK(Ca)) in a concentration-dependent manner with a half maximal concentration of 5 µmol/L. The riluzole-induced increase in outward current was not be suppressed by glibenclamide (10 µmol/L) or apamin (200 nmol/L). However, iberiotoxin (200 nmol/L) or tetrandrine (10 µmol/L) can effectively suppress riluzole-induced IK(Ca). Under inside-out patch recording mode, riluzole (10 µmol/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 µmol/L) did not affect the amplitude of voltage-dependent K+ current, but it produced a slight reduction of L-type voltage-dependent Ca2+ current. Under current clamp mode, riluzole (10 µmol/L) decreased the firing rate of action potentials induced by thyrotropin releasing hormone (10 µmol/L) in GH3 cells. In rat pheochromocytoma PC12 cells, riluzole also increased the activity of BKCa channels without altering their channel conductance.
Conclusion
This study shows that riluzole can stimulate the activity of BKCa channel in neuroendocrine cells.
Keywords
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