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;
/
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 *
                            
/*******Cerebellar Golgi Cell Model **********

Developers:    Sergio Solinas & Egidio D'Angelo
Code contributors:  Thierry Neius, Shyam Diwakar, Lia Forti
Data Analysis: Sergio Solinas

Work Progress: April 2004 - May 2007

Developed At:  Università Degli Studi Di Pavia
	       Dipartimento Di Scienze Fisiologiche
	       Pavia - Italia
	       
Model Published in: 
             Sergio M. Solinas, Lia Forti, Elisabetta Cesana, 
             Jonathan Mapelli, Erik De Schutter and Egidio D`Angelo (2008)
             Computational reconstruction of pacemaking and intrinsic 
             electroresponsiveness in cerebellar golgi cells
             Frontiers in Cellular Neuroscience 2:2


********************************************/

objref AmpaSchemeMenu,mfpanel
objref Golgi_params

xpanel("Comand Panel",0)
xmenu()
xbutton("Golgi Cell","Golgi_Panel()")
xbutton("Channels","Golgi_Channels()")
xbutton("Synapses","Postsyn_conf()") 
xbutton("Intrisic noise","Gnoise()") 
xbutton("Firing statistics","FR_show()") // FR_show is in utils.hoc
xmenu()

xpanel(1090,25,0)

proc Golgi_Panel(){
    lkg_erev = Golgi[0].soma.el_Golgi_lkg
    lkg_gbar = Golgi[0].soma.glbar_Golgi_lkg
    na_gbar = Golgi[0].soma.gnabar_Golgi_Na
    
    Golgi_params = new VBox()
	Golgi_params.intercept(1)   
	xpanel("1")  
	xlabel("Conductances")
	xvalue("gNabar","Golgi[0].soma.gnabar_Golgi_Na", 1,"", 0, 0 )
	xvalue("gNapbar","Golgi[0].soma.gbar_Golgi_NaP", 1,"", 0, 0 )
	xvalue("gNaresurgent","Golgi[0].soma.gnabar_Golgi_NaR", 1,"", 0, 0 )
	xvalue("gKVbar","Golgi[0].soma.gkbar_Golgi_KV", 1,"", 0, 0 )
	xvalue("gKAbar","Golgi[0].soma.gkbar_Golgi_KA", 1,"", 0, 0 )
	xvalue("gKCabar","Golgi[0].soma.gkbar_Golgi_BK", 1,"", 0, 0 )
	xvalue("gCaHVAbar","Golgi[0].soma.gcabar_Golgi_Ca_HVA", 1,"", 0, 0 )
	xvalue("gCaLVAbar","Golgi[0].soma.gca2bar_Golgi_Ca_LVA", 1,"", 0, 0 )
	xvalue("gKSlowbar","Golgi[0].soma.gkbar_Golgi_KM", 1,"", 0, 0 )
	xvalue("gSK2bar","Golgi[0].soma.gkbar_Golgi_SK2", 1,"", 0, 0 )
	xvalue("ghcn1bar","Golgi[0].soma.gbar_Golgi_hcn1", 1,"", 0, 0 )
	xvalue("ghcn2bar","Golgi[0].soma.gbar_Golgi_hcn2", 1,"", 0, 0 )
	xvalue("Lkg Erev (mV)","lkg_erev", 1,"UpDatelkg()", 0, 0 )
	xvalue("Lkg gbar (S/cm2)","lkg_gbar", 1,"UpDatelkg()", 0, 0 )

	
	xlabel("Passive properties: ")
	strdef stroutput
	sprint(stroutput,"K: Erev %3.0f (mV)",Golgi[0].soma.ek)
	xlabel(stroutput)
	sprint(stroutput,"Na: Erev %3.0f (mV)",Golgi[0].soma.ena)
	xlabel(stroutput)
	sprint(stroutput,"Ca: Erev %3.0f (mV)",Golgi[0].soma.eca)
	sprint(stroutput,"Cai %5.0f (nM) Cao %3.0f (mM)",Golgi[0].soma.cai*1e6,Golgi[0].soma.cao)
	xlabel(stroutput)
	sprint(stroutput,"Rm %4.0f (MOhm)",1e-6/(Golgi[0].soma.glbar_Golgi_lkg*cell_surf_cm))
	xlabel(stroutput)
	sprint(stroutput,"Cm %5.1f (pF)",Golgi[0].soma.cm*cell_surf_cm*1e6)
	xlabel(stroutput)
	
	xpanel()
	xpanel("2")
	xlabel("Calcium HVA parameters")
	xvalue("Shell thickness","Golgi[0].soma.d_Golgi_CALC", 1,"", 0, 0 )
	xvalue("Initial concentration","Golgi[0].soma.cai0_Golgi_CALC", 1,"", 0, 0 )
	xvalue("Removal rate","Golgi[0].soma.beta_Golgi_CALC", 1,"", 0, 0 ) 
	xlabel("Calcium LVA parameters")
	xvalue("Shell thickness","Golgi[0].soma.d_Golgi_CALC_ca2", 1,"", 0, 0 )
	xvalue("Initial concentration","Golgi[0].soma.ca2i0_Golgi_CALC_ca2", 1,"", 0, 0 )
	xvalue("Removal rate","Golgi[0].soma.beta_Golgi_CALC_ca2", 1,"", 0, 0 ) 
	xpanel()
	Golgi_params.intercept(0)
	Golgi_params.map("Golgi Cell Parameters", 1352, 22, 309, 742)
    }

proc Golgi_Channels() {
    xopen("Channel_dynamics.hoc")
}

proc Postsyn_conf() {
    xpanel("Synaptic paramters")
    xstatebutton("Activate synapses",&synstate ,"set_syn_start(synstate)")
    xlabel ("Excitatory synapses: 26 per dendrite")
    exc_gmax = Golgi[0].exc[0].gmax
    xvalue ("Max cond. (pS)","exc_gmax", 1,"set_exc_gmax(exc_gmax)", 0, 0 )
    xvalue ("Stim. freq. (Hz)","Exc_freq",1,"Set_Exc_freq(Exc_freq)", 0, 0 )
    xlabel ("Inhibitory synapses: 13 per dendrite")
    inh_gmax = Golgi[0].inh[0].gmax
    xvalue ("Max cond. (pS)","inh_gmax", 1,"set_inh_gmax(inh_gmax)", 0, 0 )
    xvalue ("Stim. freq. (Hz)","Inh_freq",1,"Set_Inh_freq(Inh_freq)", 0, 0 )
    xpanel()
}

proc set_syn_start(){local syn_start
    syn_start = (!$1)*1e9
    for i=0,77 {
	Exc[i].start = syn_start
    }
    for i=0,26 {
	Inh[i].start = syn_start
    }    
}

proc set_exc_gmax(){
    for i=0,77 {Golgi[0].exc[i].gmax = $1}   
}

proc set_inh_gmax(){
    for i=0,26 {Golgi[0].inh[i].gmax = $1}   
}

proc Set_Exc_freq() {
    for i=0,77 {
	Exc[i].fast_invl = 1000/$1
    }
}

proc Set_Inh_freq(){
    for i=0,26 {
	Inh[i].fast_invl = 1000/$1
    }
}

proc Gnoise() {
    xpanel("Intirsic noise")
    xstatebutton("Activate",&gnoisestate ,"set_gnoise_start(gnoisestate,gnoise)")
    xvalue("Amplitude (nA)","gauss_noise_amp", 1,"r.normal(0,gauss_noise_amp)", 0, 0 )    
    xpanel()
}

proc set_gnoise_start() {
    $o2.del = (!$1)*1e9
    $o2.dur = 100000
    $o2.amp = ($1)*1e9
    cvode.active(!$1)
}

strdef dirn

strdef KinMenu
KinMenu="kinetics.hoc"
objref Golgi_params

    
proc UpDatelkg() {
    Golgi[0].soma.el_Golgi_lkg     = lkg_erev
    for i=0,2 Golgi[0].dend[i].el_Golgi_lkg = lkg_erev
    Golgi[0].axon.el_Golgi_lkg     = lkg_erev
    
    Golgi[0].soma.glbar_Golgi_lkg     = lkg_gbar
    for i=0,2 Golgi[0].dend[i].glbar_Golgi_lkg = lkg_gbar
    Golgi[0].axon.glbar_Golgi_lkg     = lkg_gbar
        
}


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