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 h2,h3
h2 = new HBox()
h2.intercept(1)
access Golgi[0].soma

xpanel("1")
xlabel("Sodium channels")
xlabel("Na transient current activation")
Aalpha_m_NaT = Aalpha_m_Golgi_Na*tcorr_Golgi_Na
xvalue("Aalpha_m (/ms-mV)","Aalpha_m_NaT")
Abeta_m_NaT = Abeta_m_Golgi_Na*tcorr_Golgi_Na
xvalue("Abeta_m (/ms)","Abeta_m_NaT")
xvalue("V0alpha_m","V0alpha_m_Golgi_Na", 1,"", 0, 0 )
xvalue("V0beta_m","V0beta_m_Golgi_Na", 1,"", 0, 0 )
xvalue("Kalpha_m","Kalpha_m_Golgi_Na", 1,"", 0, 0 )
xvalue("Kbeta_m","Kbeta_m_Golgi_Na", 1,"", 0, 0 )
xlabel("Na transient current inactivation")
Aalpha_h_NaT = Aalpha_h_Golgi_Na*tcorr_Golgi_Na
xvalue("Aalpha_h (/ms)","Aalpha_h_NaT")
Abeta_h_NaT = Abeta_h_Golgi_Na*tcorr_Golgi_Na
xvalue("Abeta_h (/ms)","Abeta_h_NaT")
xvalue("V0alpha_h","V0alpha_h_Golgi_Na", 1,"", 0, 0 )
xvalue("V0beta_h","V0beta_h_Golgi_Na", 1,"", 0, 0 )
xvalue("Kalpha_h","Kalpha_h_Golgi_Na", 1,"", 0, 0 )
xvalue("Kbeta_h","Kbeta_h_Golgi_Na", 1,"", 0, 0 )

xlabel("Na persistent current")
Aalpha_m_NaP = Aalpha_m_Golgi_NaP * tcorr_Golgi_NaP
xvalue("Aalpha_m (/ms-mV)","Aalpha_m_NaP")
Abeta_m_NaP = Abeta_m_Golgi_NaP * tcorr_Golgi_NaP
xvalue("Abeta_m (/ms-mV)","Abeta_m_NaP")
xvalue("V0alpha_m","V0alpha_m_Golgi_NaP", 1,"", 0, 0 )
xvalue("V0beta_m","V0beta_m_Golgi_NaP", 1,"", 0, 0 )
xvalue("Kalpha_m","Kalpha_m_Golgi_NaP", 1,"", 0, 0 )
xvalue("Kbeta_m","Kbeta_m_Golgi_NaP", 1,"", 0, 0 )
xvalue("V0_minf","V0_minf_Golgi_NaP", 1,"", 0, 0 )
xvalue("K_minf","B_minf_Golgi_NaP", 1,"", 0, 0 )

xlabel("Na resurgent current activation")
Shiftalpha_s_NaR = Shiftalpha_s_Golgi_NaR*tcorr_Golgi_NaR
xvalue("Shiftalpha_s (/ms)","Shiftalpha_s_NaR")
Aalpha_s_NaR = Aalpha_s_Golgi_NaR*tcorr_Golgi_NaR
xvalue("Aalpha_s (/ms)","Aalpha_s_NaR")
Shiftbeta_s_NaR = Shiftbeta_s_Golgi_NaR*tcorr_Golgi_NaR
xvalue("Shiftbeta_s (/ms)","Shiftbeta_s_NaR")
Abeta_s_NaR = Abeta_s_Golgi_NaR*tcorr_Golgi_NaR
xvalue("Abeta_s (/ms)","Abeta_s_NaR")
xvalue("V0alpha_s","V0alpha_s_Golgi_NaR", 1,"", 0, 0 )
xvalue("V0beta_s","V0beta_s_Golgi_NaR", 1,"", 0, 0 )
xvalue("Kalpha_s","Kalpha_s_Golgi_NaR", 1,"", 0, 0 )
xvalue("Kbeta_s","Kbeta_s_Golgi_NaR", 1,"", 0, 0 )
xlabel("Na resurgent current inactivation")
Aalpha_f_NaR = Aalpha_f_Golgi_NaR*tcorr_Golgi_NaR
xvalue("Aalpha_f (/ms)","Aalpha_f_NaR")
Abeta_f_NaR = Abeta_f_Golgi_NaR*tcorr_Golgi_NaR
xvalue("Abeta_f (/ms)","Abeta_f_NaR")
xvalue("V0alpha_f","V0alpha_f_Golgi_NaR", 1,"", 0, 0 ) 
xvalue("V0beta_f","V0beta_f_Golgi_NaR", 1,"", 0, 0 )
xvalue("Kalpha_f","Kalpha_f_Golgi_NaR", 1,"", 0, 0 )
xvalue("Kbeta_f","Kbeta_f_Golgi_NaR", 1,"", 0, 0 )
xpanel(1)

xpanel("2")
xlabel("Potassium channels")
xlabel("KV current")
Aalpha_n_KV = Aalpha_n_Golgi_KV*tcorr_Golgi_KV
xvalue("Aalpha_n (/ms-mV)","Aalpha_n_KV")
Abeta_n_KV = Abeta_n_Golgi_KV*tcorr_Golgi_KV
xvalue("Abeta_n (/ms)","Abeta_n_KV")
xvalue("V0alpha_n","V0alpha_n_Golgi_KV", 1,"", 0, 0 )
xvalue("V0beta_n","V0beta_n_Golgi_KV", 1,"", 0, 0 )
xvalue("Kalpha_n","Kalpha_n_Golgi_KV", 1,"", 0, 0 )
xvalue("Kbeta_n","Kbeta_n_Golgi_KV", 1,"", 0, 0 )

xlabel("KA current activation")
Aalpha_a_KA = Aalpha_a_Golgi_KA*tcorr_Golgi_KA
xvalue("Aalpha_a (/ms)","Aalpha_a_KA")
Abeta_a_KA = Abeta_a_Golgi_KA*tcorr_Golgi_KA
xvalue("Abeta_a (/ms)","Abeta_a_KA")
xvalue("V0alpha_a","V0alpha_a_Golgi_KA", 1,"", 0, 0 )
xvalue("V0beta_a","V0beta_a_Golgi_KA", 1,"", 0, 0 )
xvalue("Kalpha_a","Kalpha_a_Golgi_KA", 1,"", 0, 0 )
xvalue("Kbeta_a","Kbeta_a_Golgi_KA", 1,"", 0, 0 )
xvalue("V0_ainf","V0_ainf_Golgi_KA", 1,"", 0, 0 )
xvalue("K_ainf","K_ainf_Golgi_KA", 1,"", 0, 0 )

xlabel("KA current inactivation")
Aalpha_b_KA = Aalpha_b_Golgi_KA*tcorr_Golgi_KA
xvalue("Aalpha_b (/ms)","Aalpha_b_KA")
Abeta_b_KA = Abeta_b_Golgi_KA*tcorr_Golgi_KA
xvalue("Abeta_b (/ms)","Abeta_b_KA")
xvalue("V0alpha_b","V0alpha_b_Golgi_KA", 1,"", 0, 0 )
xvalue("V0beta_b","V0beta_b_Golgi_KA", 1,"", 0, 0 )
xvalue("Kalpha_b","Kalpha_b_Golgi_KA", 1,"", 0, 0 )
xvalue("Kbeta_b","Kbeta_b_Golgi_KA", 1,"", 0, 0 )
xvalue("V0_binf","V0_binf_Golgi_KA", 1,"", 0, 0 )
xvalue("K_binf","K_binf_Golgi_KA", 1,"", 0, 0 )

xlabel("KM current")
Aalpha_n_KM = Aalpha_n_Golgi_KM * tcorr_Golgi_KM
xvalue("Aalpha_n (/ms)","Aalpha_n_KM")
Abeta_n_KM = Abeta_n_Golgi_KM * tcorr_Golgi_KM
xvalue("Abeta_n (/ms)","Abeta_n_KM")
xvalue("V0alpha_n","V0alpha_n_Golgi_KM", 1,"", 0, 0 )
xvalue("V0beta_n","V0beta_n_Golgi_KM", 1,"", 0, 0 )
xvalue("Kalpha_n","Kalpha_n_Golgi_KM", 1,"", 0, 0 )
xvalue("Kbeta_n","Kbeta_n_Golgi_KM", 1,"", 0, 0 )
xvalue("V0_ninf","V0_ninf_Golgi_KM", 1,"", 0, 0 )
xvalue("K_ninf","B_ninf_Golgi_KM", 1,"", 0, 0 )
xpanel()

xpanel("3")
xlabel("Calcium channels")
xlabel("Ca-HVA current activation")
Aalpha_s_HVA = Aalpha_s_Golgi_Ca_HVA*tcorr_Golgi_Ca_HVA
xvalue("Aalpha_s (/ms)","Aalpha_s_HVA")
Abeta_s_HVA = Abeta_s_Golgi_Ca_HVA*tcorr_Golgi_Ca_HVA
xvalue("Abeta_s (/ms)","Abeta_s_HVA")
xvalue("V0alpha_s","V0alpha_s_Golgi_Ca_HVA", 1,"", 0, 0 )
xvalue("V0beta_s","V0beta_s_Golgi_Ca_HVA", 1,"", 0, 0 )
xvalue("Kalpha_s","Kalpha_s_Golgi_Ca_HVA", 1,"", 0, 0 )
xvalue("Kbeta_s","Kbeta_s_Golgi_Ca_HVA", 1,"", 0, 0 )

xlabel("Ca_HVA current inactivation")
Aalpha_u_HVA = Aalpha_u_Golgi_Ca_HVA*tcorr_Golgi_Ca_HVA
xvalue("Aalpha_u (/ms)","Aalpha_u_HVA")
Abeta_u_HVA = Abeta_u_Golgi_Ca_HVA*tcorr_Golgi_Ca_HVA
xvalue("Abeta_u (/ms)","Abeta_u_HVA")
xvalue("V0alpha_u","V0alpha_u_Golgi_Ca_HVA", 1,"", 0, 0 )
xvalue("V0beta_u","V0beta_u_Golgi_Ca_HVA", 1,"", 0, 0 )
xvalue("Kalpha_u","Kalpha_u_Golgi_Ca_HVA", 1,"", 0, 0 )
xvalue("Kbeta_u","Kbeta_u_Golgi_Ca_HVA", 1,"", 0, 0 )

xlabel("Ca-LVA current activation")
xvalue("v0_m_inf","v0_m_inf_Golgi_Ca_LVA", 1,"", 0, 0 )
xvalue("k_m_inf","k_m_inf_Golgi_Ca_LVA", 1,"", 0, 0 )
	
xvalue("C_tau_m","C_tau_m_Golgi_Ca_LVA", 1,"", 0, 0 )
xvalue("A_tau_m","A_tau_m_Golgi_Ca_LVA", 1,"", 0, 0 )
xvalue("v0_tau_m1","v0_tau_m1_Golgi_Ca_LVA", 1,"", 0, 0 )
xvalue("v0_tau_m2","v0_tau_m2_Golgi_Ca_LVA", 1,"", 0, 0 )
xvalue("k_tau_m1","k_tau_m1_Golgi_Ca_LVA", 1,"", 0, 0 )
xvalue("k_tau_m2","k_tau_m2_Golgi_Ca_LVA", 1,"", 0, 0 )

xlabel("Ca-LVA current intivation")
xvalue("v0_h_inf","v0_h_inf_Golgi_Ca_LVA", 1,"", 0, 0 )
xvalue("k_h_inf","k_h_inf_Golgi_Ca_LVA", 1,"", 0, 0 )

xvalue("C_tau_h","C_tau_h_Golgi_Ca_LVA", 1,"", 0, 0 )
xvalue("A_tau_h","A_tau_h_Golgi_Ca_LVA", 1,"", 0, 0 )
xvalue("v0_tau_h1","v0_tau_h1_Golgi_Ca_LVA", 1,"", 0, 0 )
xvalue("v0_tau_h2","v0_tau_h2_Golgi_Ca_LVA", 1,"", 0, 0 )
xvalue("k_tau_h1","k_tau_h1_Golgi_Ca_LVA", 1,"", 0, 0 )
xvalue("k_tau_h2","k_tau_h2_Golgi_Ca_LVA", 1,"", 0, 0 )

xpanel()

xpanel("4")
xlabel("Potassium [Ca]-dependent channels")
xlabel("KCa current activation")
Aalpha_c_BK = Aalpha_c_Golgi_BK * tcorr_Golgi_BK
xvalue("Aalpha_c (/ms)","Aalpha_c_BK")
Abeta_c_BK = Abeta_c_Golgi_BK * tcorr_Golgi_BK
xvalue("Abeta_c (/ms)","Abeta_c_BK")
xvalue("Balpha_c","Balpha_c_Golgi_BK", 1,"", 0, 0 )
xvalue("Bbeta_c","Bbeta_c_Golgi_BK", 1,"", 0, 0 )
xvalue("Kalpha_c","Kalpha_c_Golgi_BK", 1,"", 0, 0 )
xvalue("Kbeta_c","Kbeta_c_Golgi_BK", 1,"", 0, 0 )

xlabel("SK current")
xlabel("Markov 6-state model")
dirc2t = dirc2_Golgi_SK2 * tcorr_Golgi_SK2
xvalue("c1->c2 (/ms-mM)","dirc2t")
invc1t = invc1_Golgi_SK2 * tcorr_Golgi_SK2
xvalue("c1<-c2 (/ms)","invc1t")

dirc3t = dirc3_Golgi_SK2 * tcorr_Golgi_SK2
xvalue("c2->c3 (/ms-mM)","dirc3t")
invc2t = invc2_Golgi_SK2 * tcorr_Golgi_SK2
xvalue("c2<-c3 (/ms)","invc2t")

dirc4t = dirc4_Golgi_SK2 * tcorr_Golgi_SK2
xvalue("c3->c4 (/ms-mM)","dirc4t")
invc3t = invc3_Golgi_SK2 * tcorr_Golgi_SK2
xvalue("c3<-c4 (/ms)","invc3t")

diro1t = diro1_Golgi_SK2 * tcorr_Golgi_SK2
xvalue("c3->o1 (/ms)","diro1t")
invo1t = invo1_Golgi_SK2 * tcorr_Golgi_SK2
xvalue("c3<-o1 (/ms)","invo1t")

diro2t = diro2_Golgi_SK2 * tcorr_Golgi_SK2
xvalue("c4->o2 (/ms)","diro2t")
invo2t = invo2_Golgi_SK2 * tcorr_Golgi_SK2
xvalue("c4<-o2 (/ms)","invo2t")

xpanel()

h2.intercept(0)
h2.map("Golgi Channel Kinetics")

h3 = new HBox()
h3.intercept(1)

xpanel("5")
xlabel("Hyperpolarization activated current")
xlabel("HCN1 channel")
xlabel("Fast/Slow components")
xvalue("fraction shift","rB_Golgi_hcn1")
xvalue("fraction farctor","rA_Golgi_hcn1")
xlabel("Activation")
xvalue("Vhalf","Ehalf_Golgi_hcn1")
xvalue("Slope","c_Golgi_hcn1")
xlabel("Fast time course")
xvalue("Vm factor","tCf_Golgi_hcn1")
xvalue("Vm half","tDf_Golgi_hcn1")
xvalue("Slope","tEf_Golgi_hcn1")
xlabel("Slow time course")
xvalue("Vm factor","tCs_Golgi_hcn1")
xvalue("Vm half","tDs_Golgi_hcn1")
xvalue("Slope","tEs_Golgi_hcn1")

xlabel("HCN2 channel")
xlabel("Fast/Slow components")
xvalue("fraction shift","rB_Golgi_hcn2")
xvalue("fraction farctor","rA_Golgi_hcn2")
xlabel("Activation")
xvalue("Vhalf","Ehalf_Golgi_hcn2")
xvalue("Slope","c_Golgi_hcn2")
xlabel("Fast time course")
xvalue("Vm factor","tCf_Golgi_hcn2")
xvalue("Vm half","tDf_Golgi_hcn2")
xvalue("Slope","tEf_Golgi_hcn2")
xlabel("Slow time course")
xvalue("Vm factor","tCs_Golgi_hcn2")
xvalue("Vm half","tDs_Golgi_hcn2")
xvalue("Slope","tEs_Golgi_hcn2")
xpanel()

h3.intercept(0)
h3.map("Golgi Channel Kinetics")



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