Alcohol excites Cerebellar Golgi Cells by inhibiting the Na+/K+ ATPase (Botta et al.2010)

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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.
1 . 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 35:1984-96 [PubMed]
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Model Information (Click on a link to find other models with that property)
Model Type: Neuron or other electrically excitable cell; Electrogenic pump;
Brain Region(s)/Organism: Cerebellum;
Cell Type(s): Cerebellum golgi cell;
Channel(s): Na/K pump;
Gap Junctions:
Gene(s): HCN1;
Simulation Environment: NEURON;
Model Concept(s): Detailed Neuronal Models; Markov-type model; Alcohol Use Disorder;
Implementer(s): Simoes-de-Souza, Fabio [fabio.souza at];
Search NeuronDB for information about:  Na/K pump;
Golgi_BK.mod *
Golgi_Ca_HVA.mod *
Golgi_Ca_LVA.mod *
Golgi_CALC.mod *
Golgi_CALC_ca2.mod *
Golgi_hcn1.mod *
Golgi_hcn2.mod *
Golgi_KA.mod *
Golgi_KM.mod *
Golgi_KV.mod *
Golgi_lkg.mod *
Golgi_Na.mod *
Golgi_NaP.mod *
Golgi_NaR.mod *
Golgi_SK2.mod *
K_conc.mod *
Na_conc.mod *
Pregen.mod *
Synapse.mod *
Channel_dynamics.hoc *
Golgi_ComPanel.hoc *
Save_data.hoc *
Synapses.hoc *
utils.hoc *
/*******Cerebellar Golgi Cell Model **********

Developers:    Sergio Solinas & Egidio D'Angelo
Code contributors:  Thierry Neius, Shyam Diwakar, Lia Forti
Data Analysis: Sergio Solinas

Work Progress: April 2004 - May 2007

Developed At:  Università Degli Studi Di Pavia
	       Dipartimento Di Scienze Fisiologiche
	       Pavia - Italia
Model Published in: 
             Sergio M. Solinas, Lia Forti, Elisabetta Cesana, 
             Jonathan Mapelli, Erik De Schutter and Egidio D`Angelo (2008)
             Computational reconstruction of pacemaking and intrinsic 
             electroresponsiveness in cerebellar golgi cells
             Frontiers in Cellular Neuroscience 2:2


create SynPool 
access SynPool
objref Exc[400],Inh[300]
objref list_syn_Golgi
list_syn_Golgi = new List()
synstate = 0
synstart = 1e9

Exc_freq = .53

n = 26 // Tot = 84
for j=0, 2 {
    for i=0, n-1 {
	Exc[i+(j*n)] = new Golgi_SpikeGenerator(0.5) 
	Exc[i+(j*n)].start	= 1e10
	list_syn_Golgi.append(new NetCon(Exc[i+(j*n)], Golgi[0].exc[i+(j*n)], -20, 0.000, 1e-3))
	Golgi[0].exc[i+(j*n)].gmax= 8000 // pS
	Exc[i+(j*n)].fast_invl = 1000/Exc_freq
	Exc[i+(j*n)].burst_len = 100
	Exc[i+(j*n)].noise = 1
	Exc[i+(j*n)].start = synstart

Inh_freq = 8
n = 9 // Tot=30
for j=0, 2 {
    for i=0, n-1 {
	Inh[i+(j*n)] = new Golgi_SpikeGenerator(0.5) 
	Inh[i+(j*n)].start = 1e10
	list_syn_Golgi.append(new NetCon(Inh[i+(j*n)], Golgi[0].inh[i+(j*n)], -20, 0.000, 1e-3))
	Golgi[0].inh[i+(j*n)].gmax= 16000 // pS

	Inh[i+(j*n)].fast_invl = 1000/Inh_freq
	Inh[i+(j*n)].burst_len = 100
	Inh[i+(j*n)].noise = 1
	Inh[i+(j*n)].start = synstart