Properties of aconitine-induced block of KDR current in NG108-15 neurons (Lin et al. 2008)

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Accession:112079
"The effects of aconitine (ACO), a highly toxic alkaloid, on ion currents in differentiated NG108-15 neuronal cells were investigated in this study. ACO (0.3-30 microM) suppressed the amplitude of delayed rectifier K+ current (IK(DR)) in a concentration-dependent manner with an IC50 value of 3.1 microM. The presence of ACO enhanced the rate and extent of IK(DR) inactivation, although it had no effect on the initial activation phase of IK(DR). ... A modeled cell was designed to duplicate its inhibitory effect on spontaneous pacemaking. ... Taken together, the experimental data and simulations show that ACO can block delayed rectifier K+ channels of neurons in a concentration- and state-dependent manner. Changes in action potentials induced by ACO in neurons in vivo can be explained mainly by its blocking actions on IK(DR) and INa."
Reference:
1 . Lin MW, Wang YJ, Liu SI, Lin AA, Lo YC, Wu SN (2008) Characterization of aconitine-induced block of delayed rectifier K+ current in differentiated NG108-15 neuronal cells. Neuropharmacology 54:912-23 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Neuron or other electrically excitable cell;
Brain Region(s)/Organism:
Cell Type(s): Neuroblastoma;
Channel(s): I K; I Sodium; I Potassium; I_KHT;
Gap Junctions:
Receptor(s):
Gene(s):
Transmitter(s):
Simulation Environment: XPPAUT;
Model Concept(s): Ion Channel Kinetics; Simplified Models; Action Potentials; Methods;
Implementer(s): Wu, Sheng-Nan [snwu at mail.ncku.edu.tw]; Lin, Ming-Wei ; Wan, Ya-Jean ; Lin, An-An ;
Search NeuronDB for information about:  I K; I Sodium; I Potassium; I_KHT;
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NG108-ACO
readme.html
ACO-NP01.pdf
Fig8A.JPG
NG108_Acon.ode
                            
# NG108_Acon.ode
# 
# IK(erg) was incorporated into the model.
# Ref: Lin et al., Neuropharmacology 2008;
# 

# Initial values of the variables
initial V=-63, A_na=0.2, inhibitedA=1.0, D=0.1, inhibitedD=0.2, m1=0.0, m=0.0, h=0.0, n1=0.0, h1=0.0, n=0.0
init nIR=0.003, rIR=0.282, h2=0.9

# Values of the model parameters: kio=k-1; koi=k+1 shown in the article
param  g_Na=60.0, g_Ca_L=1.1, g_Ca_T=0.94, g_K_dr=20.0, g_M=4.0,  g_ir=1.71, g_d=0.0277
param kio=0.00132, koi=0.00111
param ACO=0.001
param V_K=-75
number  V_Na=60.0, V_Ca=100.0, Vh=-40.0
number k1=0.3, k1_=0.03, k3=0.001, k3_=0.01
param  tau_h=22.0, tau_h1=1000.0, Cm=14.0
param girbar=50

# Kinetic equations
alpha= (10.0 / (1.0 + exp( - (0.1 * (6.0 + V)))))
beta= (10.0 / (1.0 + exp((0.2173913043478261 * (54.4 + V)))))
m_inf= (1.0 / (1.0 + exp( - (0.1 * (-56.1 + V)))))
m_inf1= (1.0 / (1.0 + exp( - (0.08333333333333333 * (V - Vh)))))
h_inf= (1.0 / (1.0 + exp((0.2127659574468085 * (86.4 + V)))))
n_inf= (1.0 / (1.0 + exp( - (0.25 * (37.0 + V)))))
n_inf1= (0.2 + (0.8 / (1.0 + exp((0.08333333333333333 * (80.0 + V))))))
n_inf2= (1.0 / (1.0 + exp( - (0.06666666666666667 * (25.0 + V)))))
h_inf1= (0.3 + (0.7 / (1.0 + exp( - (0.1 * (35.0 + V))))))
alphaIRn = 0.09/(1+exp(0.11*(V+50)))
betaIRn = 0.00035*exp(0.07*(V+25))
nIRinf = 1/(1+alphaIRn/betaIRn)
tauIRn = 1/(alphaIRn + betaIRn)
alphaIRr = 30/(1+exp(0.04*(V+245)))
betaIRr = 0.15/(1+exp(-0.05*(V+120)))
rIRinf = 1/(1+betaIRr/alphaIRr)
tauIRr = 1/(alphaIRr + betaIRr)
tau_n= (80.0 / (exp((0.06666666666666667 * (30.0 + V))) + exp( - (0.06666666666666667 * (30.0 + V)))))
tau_m= (0.8 + (7.0 / (exp((0.1111111111111111 * (50.0 + V))) + exp( - (0.1111111111111111 * (50.0 + V))))))
tau_n1= (1.0 + (15.0 / (exp((0.06666666666666667 * (30.0 + V))) + exp( - (0.06666666666666667 * (30.0 + V))))))
tau_m1= (5.0 / (exp((0.04 * (15.0 + V))) + exp( - (0.04 * (15.0 + V)))))
a= (k1 * k3_ / (k1_ * k3))^0.5
O= A_na^3

i_Na= (g_Na * O * (V - V_Na))
i_Ca_L= (g_Ca_L * m1^2 * (V - V_Ca))
i_Ca_T= (g_Ca_T * m^2 * h * (V - V_Ca))
i_K_dr= (g_K_dr * n1^4 * h1 * h2 * (V - V_K))
i_M= (g_M * n * (V - V_K))
iir=(g_ir)*n_inf1*(V-V_K)
i_d= (g_d * (V - V_Ca))
iKir=girbar*nIR*rIR*(V - V_K)

# Differential equations
V'=(-(i_Na + i_Ca_L + i_Ca_T + i_K_dr + i_M + iir + i_d + iKir) / Cm)
A_na'= D*alpha+inhibitedA*k1_-A_na*(beta+k1)
inhibitedA'=A_na*k1+inhibitedD*alpha*a-inhibitedA*(k1_+beta*a)
inhibitedD'=inhibitedA*beta*a+D*k3-inhibitedD*(alpha*a+k3_)
D'=A_na*beta+inhibitedD*k3_-D*(alpha+k3)
m1'=((m_inf1 - m1) / tau_m1)
m'=((m_inf - m) / tau_m)
h'=((h_inf - h) / tau_h)
n1'=((n_inf2 - n1) / tau_n1)
h1'=((h_inf1 - h1) / tau_h1)
n'=((n_inf - n) / tau_n)
nIR' = (nIRinf - nIR)/tauIRn
rIR' = (rIRinf - rIR)/tauIRr
h2'= kio*(1-h2)-koi*ACO*n^4*h2

aux ina=i_Na
aux iKdr=i_K_dr

# Numerical and plotting parameters for xpp
@ maxstor=800000, total=10000, bound=100000, dt=0.1
@ xlo=0, xhi=10000, ylo=-80, yhi=45
@ method=cvode, atol=0.0001, toler=0.0001

done

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