Excitation of rat cerebellar Golgi cells by ethanol : further characterization of the mechanismExcitation of rat cerebellar Golgi cells by ethanol : further characterization of the mechanism
Souza, de, Fabio M. Simões
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences . Biomedical Sciences
2012Baltimore, Md, 2012
Alcoholism: clinical and experimental research / American Medical Society on Alcoholism and other Drug Dependencies. - Baltimore, Md
36(2012):4, p. 616-624
University of Antwerp
Background: Studies with rodents suggest that acute ethanol exposure impairs information flow through the cerebellar cortex, in part, by increasing GABAergic input to granule cells. Experiments suggest that an increase in the excitability of specialized GABAergic interneurons that regulate granule cell activity (i.e., Golgi cells [GoCs]) contributes to this effect. In GoCs, ethanol increases spontaneous action potential firing frequency, decreases the afterhyperpolarization amplitude, and depolarizes the membrane potential. Studies suggest that these effects could be mediated by inhibition of the Na+/K+ ATPase. The purpose of this study was to characterize the potential role of other GoC conductances in the mechanism of action of ethanol. Methods: Computer modeling techniques and patch-clamp electrophysiological recordings with acute slices from rat cerebella were used for these studies. Results: Computer modeling suggested that modulation of subthreshold Na+ channels, hyperpolarization-activated currents, and several K+ conductances could explain some but not all actions of ethanol on GoCs. Electrophysiological studies did not find evidence consistent with a contribution of these conductances. Quinidine, a nonselective blocker of several types of channels (including several K+ channels) that also antagonizes the Na+/K+ ATPase, reduced the effect of ethanol on GoC firing. Conclusions: These findings further support that ethanol increases GoC excitability via modulation of the Na+/K+ ATPase and suggest that a quinidine-sensitive K+ channel may also play a role in the mechanism of action of ethanol.