title: Excitation of rat cerebellar Golgi cells by ethanol: further characterization of the mechanism.
abstract: 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.
authors: Department of Neurosciences, School of Medicine, University of New Mexico Health Sciences Center, Albuquerque, USA.
authors: Paolo
authors: P
authors: Botta
authors: Fabio M
authors: FM
authors: Simões de Souza
authors: Thomas
authors: T
authors: Sangrey
authors: Erik
authors: E
authors: De Schutter
authors: C Fernando
authors: CF
authors: Valenzuela
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D002531:Cerebellum / Q000166:cytology* / Q000187:drug effects*; D003198:Computer Simulation; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology*; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007395:Interneurons / Q000187:drug effects*; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000187:drug effects; D008297:Male; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects; D017966:Pyramidal Cells / Q000187:drug effects; D051381:Rats; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000187:drug effects; D015222:Sodium Channels / Q000187:drug effects; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D013268:Stimulation, Chemical
chemical_list: D002492:Central Nervous System Depressants; D054815:Cyclic Nucleotide-Gated Cation Channels; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D051036:Large-Conductance Calcium-Activated Potassium Channels; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D051640:Small-Conductance Calcium-Activated Potassium Channels; D015222:Sodium Channels; D000431:Ethanol; D000254:Sodium-Potassium-Exchanging ATPase