INHIBITION BY RILUZOLE OF GLYCINERGIC POSTSYNAPTIC CURRENTS IN RAT HYPOGLOSSAL MOTONEURONS

1 Riluzole has been shown to have beneficial effects in motoneurone di sease, yet its effect on motoneurones is not known. To address this qu estion, we investigated synaptic modulation by riluzole in hypoglossal motoneurones by recording glycinergic inhibitory postsynaptic current s evoked by stimulation of nearby single interneurones. 2 Glycinergic inhibitory postsynaptic currents were evoked by electrical stimulation of single interneurones and were recorded from visually identified hy poglossal motoneurones. Riluzole (10 mu M) inhibited mean amplitude of evoked glycinergic inhibitory postsynaptic currents by 87%. 3 We foun d that riluzole suppressed sodium currents in brainstem interneurones by 23.8%. Riluzole did not modulate barium currents through voltage-ac tivated calcium channels (98% of control). Therefore, the effect of ri luzole on synaptic transmission may be mediated, in part, by stabilizi ng presynaptic neurones through inhibition of voltage-activated sodium currents. 4 In the presence of tetrodotoxin (0.5 mu M), riluzole redu ced the frequency (1.2 Hz in control to 0.6 Hz in riluzole) of spontan eous transmitter release recorded in motoneurones. 5 Riluzole was foun d to have no effect on mean miniature inhibitory postsynaptic current amplitude, therefore the reduction in spontaneous transmitter release cannot be due to an action on postsynaptic glycine receptors. 6 We con clude that riluzole inhibits synaptic transmission presynaptically, in dependent of a reduction in the excitation of presynaptic neurones.