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
        KCa channel
   
	Author: E.DAngelo, T.Nieus, A. Fontana
	Last revised: 8.5.2000
ENDCOMMENT
 
NEURON { 
	SUFFIX Golgi_BK
	USEION k READ ek WRITE ik 
	USEION ca READ cai
	RANGE gkbar, ik, g
	RANGE Aalpha_c, Balpha_c, Kalpha_c, alpha_c, beta_c
	RANGE Abeta_c, Bbeta_c, Kbeta_c 
	RANGE c_inf, tau_c, c, tcorr
} 
 
UNITS { 
	(mA) = (milliamp) 
	(mV) = (millivolt) 
	(molar) = (1/liter)
	(mM) = (millimolar)
} 
 
PARAMETER { 
	Aalpha_c = 7 (/ms)
	Balpha_c = 1.5e-3 (mM)

	Kalpha_c =  -11.765 (mV)

	Abeta_c = 1 (/ms)
	Bbeta_c = 0.15e-3 (mM)

	Kbeta_c = -11.765 (mV)

	v (mV) 
	cai (mM)
	gkbar= 0.003 (mho/cm2) 
	ek (mV)
	celsius (degC) 
	Q10 = 3		(1)
} 

STATE { 
	c 
} 

ASSIGNED { 
	ik (mA/cm2) 
	ica (mA/cm2)

	c_inf 
	tau_c (ms) 
	g (mho/cm2) 
	alpha_c (/ms) 
	beta_c (/ms)
	tcorr (1)
} 
 
INITIAL { 
	rate(v) 
	c = c_inf 
} 
 
BREAKPOINT { 
	SOLVE states METHOD derivimplicit 
	g = gkbar*c 
	ik = g*(v - ek) 
	alpha_c = alp_c(v) 
	beta_c = bet_c(v) 
} 
 
DERIVATIVE states { 
	rate(v) 
	c' =(c_inf - c)/tau_c 
} 
 
FUNCTION alp_c(v(mV))(/ms) { 
	tcorr = Q10^((celsius-30(degC))/10(degC))
	alp_c = tcorr*Aalpha_c/(1+(Balpha_c*exp(v/Kalpha_c)/cai)) 
} 
 
FUNCTION bet_c(v(mV))(/ms) {
	tcorr = Q10^((celsius-30(degC))/10(degC))
	bet_c = tcorr*Abeta_c/(1+cai/(Bbeta_c*exp(v/Kbeta_c))) 
} 
 
PROCEDURE rate(v (mV)) {LOCAL a_c, b_c 
	a_c = alp_c(v)  
	b_c = bet_c(v) 
	tau_c = 1/(a_c + b_c) 
	c_inf = a_c/(a_c + b_c) 
}

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