The effects of Riluzole on sensory and motor nerve function

Department of Biology, University of Kentucky, Lexington, KY, USA 40506

The only Food and Drug Administration approved drug for amyotrophic lateral sclerosis (ALS) is Riluzole (Rilutek). However, the diverse mechanisms of how Riluzole functions physiologically are still being discovered. ALS is characterized by the progressive degeneration of motor neurons in the central nervous system. One approach in treating ALS is to reduce the glutamatergic excitotoxicity of the postsynaptic motor neurons. This is achieved by decreasing the activity of these motor neurons, reducing the influx of calcium into the neuron. Riluzole has been shown to antagonize presynaptic NMDA receptors mediated responses as well as directly block neuronal voltage gated Na+ and Ca2+ channels. Glutamate release inhibitors, such as Riluzole, which act as therapeutics for ALS and Huntington’s may have both pre-and postsynaptic mechanisms which are still being investigated. Here, experimental models included both glutamatergic synapses at the crayfish neuromuscular junctions (NMJs) and sensory neurons of crabs. The goal of this study was to determine if Riluzole had a direct effect on sensory neurons independent of synaptic properties and to determine if synaptic transmission is altered at glutamatergic synapses. The exposure of 1 mM Riluzole to the crayfish NMJs, at first, promotes synaptic transmission and then depresses synaptic transmission by blocking presynaptic function. The effects did not reverse readily with removal of Riluzole. We expected Riluzole to decreased the action potential amplitude in the motor neurons by blocking voltage gated Na+ and Ca2+ channels. Proprioceptive sensory neurons in the crab were not affected by 1 mM Riluzole over the same time frame. Reproducibility in analysis was accomplished by using given data sets and having various participants analyze the responses. The trends reported were similar among different participants, but absolute values were different depending on the amplitude of the extracellular signals chosen as events.

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