Patch-clamp in cerebellar slices and computer modeling show that ethanol excites Golgi cells by inhibiting the Na+/K+ ATPase. In particular, voltage-clamp recordings of Na+/K+ ATPase currents indicated that ethanol partially inhibits this pump and this effect could be mimicked by low concentrations of the Na+/K+ ATPase blocker ouabain. The partial inhibition of Na+/K+ ATPase in a computer model of the Golgi cell reproduced these experimental findings that established a novel mechanism of action of ethanol on neural excitability.
Model Type: Neuron or other electrically excitable cell; Electrogenic pump
Region(s) or Organism(s): Cerebellum
Cell Type(s): Cerebellum golgi cell
Currents: Na/K pump
Genes: HCN1
Model Concept(s): Detailed Neuronal Models; Markov-type model; Alcohol Use Disorder
Simulation Environment: NEURON
Implementer(s): Simoes-de-Souza, Fabio [fabio.souza at ufabc.edu.br]
References:
Botta P, de Souza FM, Sangrey T, De Schutter E, Valenzuela CF. (2010). Alcohol excites cerebellar Golgi cells by inhibiting the Na+/K+ ATPase. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 35 [PubMed]