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

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Accession:127021
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.
Reference:
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]
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:
Receptor(s):
Gene(s): HCN1;
Transmitter(s):
Simulation Environment: NEURON;
Model Concept(s): Detailed Neuronal Models; Markov-type model; Alcohol Use Disorder;
Implementer(s): Simoes-de-Souza, Fabio [fabio.souza at ufabc.edu.br];
Search NeuronDB for information about:  Na/K pump;
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Golgi_cell_NaKATPAse
sessions
README.html
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 *
pump.mod
Synapse.mod *
Channel_dynamics.hoc *
Golgi_ComPanel.hoc *
Golgi_count.txt
Golgi_Pump_Ouabain.ses
Golgi_template.hoc
mosinit.hoc
nerst
Save_data.hoc *
Screenshot20100716_4.02.55PM.png
Start_Golgi_Ouabain.hoc
Synapses.hoc *
utils.hoc *
                            
TITLE Cerebellum Golgi Cell Model

COMMENT
        Calcium first order kinetics
   
	Author: A. Fontana
	Revised: 12.12.98
ENDCOMMENT

NEURON {
        SUFFIX Golgi_CALC_ca2
        USEION ca2 READ ica2, ca2o WRITE ca2i VALENCE 2
        RANGE d, beta, ca2i0, ca2_pump_i
}

UNITS {
        (mV)    = (millivolt)
        (mA)    = (milliamp)
	(um)    = (micron)
	(molar) = (1/liter)
        (mM)    = (millimolar)
   	F      = (faraday) (coulomb)
}

PARAMETER {
        ica2             (mA/cm2)
        celsius    (degC)
        d = .2          (um)
        ca2o        (mM)         
        ca2i0     (mM)         
        beta = 1.3        (/ms)
}
ASSIGNED {
	ca2_pump_i	(mA)
}

STATE {
	ca2i (mM)
}

INITIAL {
        ca2i = ca2i0 
}

BREAKPOINT {
       SOLVE conc METHOD derivimplicit
}

DERIVATIVE conc {    
	:  outward ionic current with valence 2+
	ca2_pump_i = 2*beta*(ca2i-ca2i0)
	:  total outward Ca2 current
	ca2i' = -ica2/(2*F*d)*(1e4) - beta*(ca2i-ca2i0)
}



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