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 Granule Cell Model

COMMENT
        CaHVA channel
   
	Author: E.DAngelo, T.Nieus, A. Fontana
	Last revised: 8.5.2000
ENDCOMMENT
 
NEURON { 
	SUFFIX Golgi_Ca_HVA
	USEION ca READ eca WRITE ica 
	RANGE gcabar, ica, g
	:RANGE alpha_s, beta_s, alpha_u, beta_u 
	:RANGE Aalpha_s, Kalpha_s, V0alpha_s
	:RANGE Abeta_s, Kbeta_s, V0beta_s
	:RANGE Aalpha_u, Kalpha_u, V0alpha_u
	:RANGE Abeta_u, Kbeta_u, V0beta_u
	RANGE s_inf, tau_s, u_inf, tau_u
	RANGE s, u, tcorr
} 
 
UNITS { 
	(mA) = (milliamp) 
	(mV) = (millivolt) 
} 
 
PARAMETER {
	Aalpha_s = 0.04944 (/ms)
	Kalpha_s =  15.87301587302 (mV)
	V0alpha_s = -29.06 (mV)
	
	Abeta_s = 0.08298 (/ms)
	Kbeta_s =  -25.641 (mV)
	V0beta_s = -18.66 (mV)

	Aalpha_u = 0.0013 (/ms)
	Kalpha_u =  -18.183 (mV)
	V0alpha_u = -48 (mV)
		
	Abeta_u = 0.0013 (/ms)
	Kbeta_u =   83.33 (mV)
	V0beta_u = -48 (mV)

	v (mV) 
	gcabar= 460e-6 (mho/cm2) 
	eca (mV) 
	celsius (degC)
	Q10 = 3 
} 

STATE { 
	s 
	u 
} 

ASSIGNED { 
	ica (mA/cm2) 
	s_inf 
	u_inf 
	tau_s (ms) 
	tau_u (ms) 
	g (mho/cm2) 
	alpha_s (/ms)
	beta_s (/ms)
	alpha_u (/ms)
	beta_u (/ms)
	tcorr	(1)
} 
 
INITIAL { 
	rate(v) 
	s = s_inf 
	u = u_inf 
} 
 
BREAKPOINT { 
	SOLVE states METHOD derivimplicit 
	g = gcabar*s*s*u 
	ica = g*(v - eca) 
	alpha_s = alp_s(v)
	beta_s = bet_s(v)
	alpha_u = alp_u(v)
	beta_u = bet_u(v)
}
 
DERIVATIVE states { 
	rate(v) 
	s' =(s_inf - s)/tau_s 
	u' =(u_inf - u)/tau_u 
} 

FUNCTION alp_s(v(mV))(/ms) { 
	tcorr = Q10^((celsius-20(degC))/10(degC))
	alp_s = tcorr*Aalpha_s*exp((v-V0alpha_s)/Kalpha_s) 
} 
 
FUNCTION bet_s(v(mV))(/ms) { 
	tcorr = Q10^((celsius-20(degC))/10(degC))
	bet_s = tcorr*Abeta_s*exp((v-V0beta_s)/Kbeta_s) 
} 
 
FUNCTION alp_u(v(mV))(/ms) { 
	tcorr = Q10^((celsius-20(degC))/10(degC))
	alp_u = tcorr*Aalpha_u*exp((v-V0alpha_u)/Kalpha_u) 
} 
 
FUNCTION bet_u(v(mV))(/ms) { 
	tcorr = Q10^((celsius-20(degC))/10(degC))
	bet_u = tcorr*Abeta_u*exp((v-V0beta_u)/Kbeta_u) 
} 
 
PROCEDURE rate(v (mV)) {LOCAL a_s, b_s, a_u, b_u 
	TABLE s_inf, tau_s, u_inf, tau_u 
	DEPEND Aalpha_s, Kalpha_s, V0alpha_s, 
	       Abeta_s, Kbeta_s, V0beta_s,
               Aalpha_u, Kalpha_u, V0alpha_u,
               Abeta_u, Kbeta_u, V0beta_u, celsius FROM -100 TO 30 WITH 13000 
	a_s = alp_s(v)  
	b_s = bet_s(v) 
	a_u = alp_u(v)  
	b_u = bet_u(v) 
	s_inf = a_s/(a_s + b_s) 
	tau_s = 1/(a_s + b_s) 
	u_inf = a_u/(a_u + b_u) 
	tau_u = 1/(a_u + b_u) 
}


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