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

 Download zip file   Auto-launch 
Help downloading and running models
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;
/
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
        Na persistent channel
   
	Author: E.D Angelo, T.Nieus, A. Fontana 
	Last revised: 8.5.2000
ENDCOMMENT
 
NEURON { 
	SUFFIX Golgi_NaP 
	USEION na READ ena WRITE ina 
	RANGE gbar, ina, g
	:RANGE Aalpha_m, Kalpha_m, V0alpha_m, alpha_m, beta_m
	:RANGE Abeta_m, Kbeta_m, V0beta_m
	:RANGE V0_minf, B_minf
	RANGE m, m_inf, tau_m, tcorr
	:GLOBAL i
} 
 
UNITS { 
	(mA) = (milliamp) 
	(mV) = (millivolt) 
} 
 
PARAMETER { 
	gbar		= 0.00019 (mho/cm2)
	Aalpha_m 	= -0.91 (/mV-ms)
	Kalpha_m 	= -5 (mV)
	V0alpha_m 	= -40 (mV)
	Abeta_m 	= 0.62 (/mV-ms)
	Kbeta_m 	= 5 (mV)
	V0beta_m 	= -40 (mV)
	V0_minf 	= -43 (mV)
	B_minf 		= 5 (mV)
	v (mV) 
	ena 	 (mV) 
	celsius  (degC) 
	Q10 = 3	(1)
} 

STATE { 
	m 
} 

ASSIGNED { 
	ina (mA/cm2) 
	m_inf 
	tau_m (ms) 
	g (mho/cm2) 
	alpha_m (/ms)
	beta_m (/ms)
	tcorr	(1)
} 
 
INITIAL { 
	rate(v) 
	m = m_inf 
} 
 
BREAKPOINT { 
	SOLVE states METHOD derivimplicit 
	g = gbar*m 
	ina = g*(v - ena) 
	alpha_m = alp_m(v)
	beta_m = bet_m(v)
} 
 
DERIVATIVE states { 
	rate(v) 
	m' =(m_inf - m)/tau_m 
} 

FUNCTION alp_m(v(mV))(/ms) {
	tcorr = Q10^((celsius-30(degC))/10(degC))
	alp_m = tcorr * Aalpha_m*linoid(v-V0alpha_m, Kalpha_m) 
} 
 
FUNCTION bet_m(v(mV))(/ms) {
	tcorr = Q10^((celsius-30(degC))/10(degC))
	bet_m = tcorr * Abeta_m*linoid(v-V0beta_m, Kbeta_m) 
} 
 
PROCEDURE rate(v (mV)) {LOCAL a_m, b_m 
	TABLE m_inf, tau_m 
	DEPEND Aalpha_m, Kalpha_m, V0alpha_m, 
	       Abeta_m, Kbeta_m, V0beta_m, celsius FROM -100 TO 30 WITH 13000
	a_m = alp_m(v)  
	b_m = bet_m(v) 
:	m_inf = a_m/(a_m + b_m) 
	m_inf = 1/(1+exp(-(v-V0_minf)/B_minf))
	tau_m = 5/(a_m + b_m) 
} 

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)
        }
}



Loading data, please wait...