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
        KDr channel
	Gutfreund parametrization
   
	Author: A. Fontana
	Last revised: 12.12.98
ENDCOMMENT

NEURON { 
	SUFFIX Golgi_KV 
	USEION k READ ek WRITE ik 
	RANGE gkbar, ik, g
	:RANGE Aalpha_n, Kalpha_n, V0alpha_n, alpha_n, beta_n 
	:RANGE Abeta_n, Kbeta_n, V0beta_n
	RANGE n, n_inf, tau_n, tcorr
} 
 
UNITS { 
	(mA) = (milliamp) 
	(mV) = (millivolt) 
} 
 
PARAMETER { 
	
	Aalpha_n = -0.01 (/ms-mV)
	Kalpha_n = -10 (mV)
	V0alpha_n = -26 (mV)

	Abeta_n = 0.125 (/ms)
	Kbeta_n = -80 (mV)
	V0beta_n = -36 (mV)
	v (mV)  
	gkbar= 0.032 (mho/cm2)

	ek (mV) 
	celsius (degC)
	Q10 = 3 (1)
} 

STATE { 
	n 
} 

ASSIGNED { 
	ik (mA/cm2) 
	n_inf 
	tau_n (ms) 
	g (mho/cm2) 
	alpha_n (/ms) 
	beta_n (/ms)
	tcorr	(1) 
} 
 
INITIAL { 
	rate(v) 
	n = n_inf 
} 
 
BREAKPOINT { 
	SOLVE states METHOD derivimplicit 
	g = gkbar*n*n*n*n 
	ik = g*(v - ek) 
	alpha_n = alp_n(v) 
	beta_n = bet_n(v) 
} 
 
DERIVATIVE states { 
	rate(v) 
	n' =(n_inf - n)/tau_n 
} 
 
FUNCTION alp_n(v(mV))(/ms) {
	tcorr = Q10^((celsius-6.3(degC))/10(degC)) 
	alp_n = tcorr*Aalpha_n*linoid(v-V0alpha_n, Kalpha_n)
} 
 
FUNCTION bet_n(v(mV))(/ms) {
	tcorr = Q10^((celsius-6.3(degC))/10(degC)) 
	bet_n = tcorr*Abeta_n*exp((v-V0beta_n)/Kbeta_n) 
} 
 
PROCEDURE rate(v (mV)) {LOCAL a_n, b_n 
	TABLE n_inf, tau_n 
	DEPEND Aalpha_n, Kalpha_n, V0alpha_n, 
               Abeta_n, Kbeta_n, V0beta_n, celsius FROM -100 TO 30 WITH 13000 
	a_n = alp_n(v)  
	b_n = bet_n(v) 
	tau_n = 1/(a_n + b_n) 
	n_inf = a_n/(a_n + b_n) 
} 

FUNCTION linoid(x (mV),y (mV)) (mV) {
        if (fabs(x/y) < 1e-6) {
                linoid = y*(1 - x/y/2)
        }else{
                linoid = x/(exp(x/y) - 1)
        }
}

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