Computational Insights into the Neuroprotective Action of Riluzole on 3-Acetylpyridine-Induced Ataxia in Rats

Objective: intra-peritoneal administration of riluzole has been shown to preserve themembrane properties and firing characteristics of purkinje neurons in a rat model of cer- ebellar ataxia induced by 3-acetylpyridine (3-ap). however, the exact mechanism(s) by which riluzole restores the normal electrophysiological properties of purkinje neurons is not completely understood. changes in the conductance of several ion channels, includ- ing the bk channels, have been proposed as a neuro protective target of riluzole. in this study, the possible cellular effects of riluzole on purkinje cells from 3-ap-induced ataxic rats that could be responsible for its neuro protective action have been investigated by computer simulations.materials and methods: this is a computational stimulation study. the simulation envi- ronment enabled a change in the properties of the specific ion channels as the possible mechanism of action of riluzole. this allowed us to study the resulted changes in the firing activity of purkinje cells without concerns about its other effects and interfering param- eters in the experiments. simulations were performed in the neuron environment (ver- sion 7.1) in a time step of 25 ?s; analyses were conducted using matlab r2010a (the mathworks). data were given as mean ± sem. statistical analyses were performed by the student's t test, and differences were considered significant if p < o.os. results: the computational findings demonstrated that modulation of an individual ion channel current, as suggested by previous experimental studies, should not be consid- ered as the only possible target for the neuro protective effects of riluzole to restore the normal firing activity of purkinje cells from ataxic rats.conclusion: changes in the conductance of several potassium channels, including volt- age-gated potassium (kv1, kv4) and big ca2+-activated k+ (bk) channels may be respon- sible for the neuro protective effect of riluzole against 3-ap induced alterations in the firing properties of purkinje cells in a rat model of ataxia.