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 Synapse C=O gating scheme

COMMENT
Synaptic model C=O gating scheme.
tau_1, tau_2 are the binding and unbinding time constants.

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
ENDCOMMENT

NEURON {
	POINT_PROCESS Synapse
	NONSPECIFIC_CURRENT i	
	RANGE g,gmax, Cdur,Erev 
	RANGE tau_1,tau_2
}

UNITS {
	(nA) = (nanoamp)
	(mV) = (millivolt)	
	(mM) = (milli/liter)
	(pS) = (picosiemens)
	(nS) = (nanosiemens)
	(um) = (micrometer)
	PI   = (pi)(1)
}

PARAMETER {
	:  Postsynaptic parameters
	tau1		= .4		(/ms/mM) 	 
        tau2		= 3		(/ms)
        gmax		= 1150 		(pS)
	Cdur		= 0.3		(ms)		 
	Erev		= 0		(mV)
	Tmax		= 1  (mM)
}


ASSIGNED {
	v		(mV)		: postsynaptic voltage
	i 		(nA)		: current = g*(v - Erev)
	g 		(pS)		: conductance
	r1		(/ms)
	T		(mM)
	ton		(ms)	
	
}

STATE {	
	C
	O
}	
	

INITIAL {
	C		=	1
	O		=	0
	T		=	0 	(mM)
	ton		=  	-1   (ms)
}

BREAKPOINT {
	SOLVE kstates METHOD sparse
	g =gmax * O
	i = (1e-6) * g * (v - Erev) : 1e-6 fA=>nA
}


KINETIC kstates {
	: Postsynaptic scheme
	r1 = 1/tau1 * T
	~ C  <-> O	(r1,1/tau2)
	CONSERVE C+O = 1
}


NET_RECEIVE(weight, on, nspike, t0 (ms), tsyn (ms)) {
	INITIAL {
		nspike = 1
		tsyn=t
	}
   	if (flag == 0) { 
		nspike = nspike + 1
		if (!on) {
			ton=t
			t0=t
			on=1				
		        T=Tmax
			tsyn=t						
		}
		net_send(Cdur,nspike)
    	}
	if(flag==nspike){ 		
		T = 0
		on = 0
	}
}	 

 

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