Inhibition by riluzole of glycinergic postsynaptic currents in rat hypoglossal motoneurones.
1. Riluzole has been shown to have beneficial effects in motoneurone disease, yet its effect on motoneurones is not known. To address this question, we investigated synaptic modulation by riluzole in hypoglossal motoneurones by recording glycinergic inhibitory postsynaptic currents 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 hypoglossal motoneurones. Riluzole (10 microM) inhibited mean amplitude of evoked glycinergic inhibitory postsynaptic currents by 87%. 3. We found that riluzole suppressed sodium currents in brainstem interneurones by 23.8%. Riluzole did not modulate barium currents through voltage-activated calcium channels (98% of control). Therefore, the effect of riluzole on synaptic transmission may be mediated, in part, by stabilizing presynaptic neurones through inhibition of voltage-activated sodium currents. 4. In the presence of tetrodotoxin (0.5 microM), riluzole reduced the frequency (1.2 Hz in control to 0.6 Hz in riluzole) of spontaneous transmitter release recorded in motoneurones. 5. Riluzole was found 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 conclude that riluzole inhibits synaptic transmission presynaptically, independent of a reduction in the excitation of presynaptic neurones.
Umemiya
M
M
Department of Physiology and Biophysics, School of Medicine, University of Washington, Seattle 98195, USA.
Berger
A J
AJ
D000818:Animals; D000831:Animals, Newborn; D018684:Glycine Agents / Q000494:pharmacology*; D007002:Hypoglossal Nerve / Q000187:drug effects*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects*; D009046:Motor Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019782:Riluzole; D009435:Synaptic Transmission / Q000187:drug effects; D013779:Tetrodotoxin / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology*
D018684:Glycine Agents; D007473:Ion Channels; D018696:Neuroprotective Agents; D013844:Thiazoles; D013779:Tetrodotoxin; D019782:Riluzole