Action potential of adult rat ventricle (Wang et al. 2008)

 Download zip file 
Help downloading and running models
Accession:120246
"Aconitine (ACO), a highly toxic diterpenoid alkaloid, is recognized to have effects on cardiac voltage-gated Na(+) channels. However, it remains unknown whether it has any effects on K(+) currents. The effects of ACO on ion currents in differentiated clonal cardiac (H9c2) cells and in cultured neonatal rat ventricular myocytes were investigated in this study. ..." The rat action potential in this simulation was played back into the cell for experiments reported in this paper.
Reference:
1 . Wang YJ, Chen BS, Lin MW, Lin AA, Peng H, Sung RJ, Wu SN (2008) Time-dependent block of ultrarapid-delayed rectifier K+ currents by aconitine, a potent cardiotoxin, in heart-derived H9c2 myoblasts and in neonatal rat ventricular myocytes. Toxicol Sci 106:454-63 [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): Cardiac ventricular cell;
Channel(s):
Gap Junctions:
Receptor(s):
Gene(s):
Transmitter(s):
Simulation Environment: XPP;
Model Concept(s): Action Potentials;
Implementer(s): Wu, Sheng-Nan [snwu at mail.ncku.edu.tw];
/
RatAP
readme.html
RatAP.JPG
RatAPtest01.ode
                            
# RatAPtest01.ode
# Rat action potential is simulated (bondarenko_model_2004)
# (cf. Bondarenko et al. Am J Physiol Heart Circ Physiol 2004;287: H1378-H1403)
# (cf. Wang et al. Toxicol Sci 2008;106:454-463)
# implemented by Dr. Sheng-Nan Wu

# Constant values
Number  Temp=298.0, R=8.314, Fara=96.5
Number  E_CaL=63.0, E_Cl=-40.0
Number Cm=1.0, Vmyo=2.584E-5, VNSR=2.098E-6, VJSR=1.2E-7

# Initial values
Initial V=-82.4202, Cai=0.115001
Initial Nai=14237.1, Ki=143720.0
Initial C_Na1=2.79132E-4, C_Na2=0.020752, O_Na=7.13483E-7
Initial IF_Na=1.53176E-4, I1_Na=6.73345E-7, I2_Na=1.55787E-9
Initial IC_Na2=0.0113879, IC_Na3=0.34278
Initial ato_f=0.00265563, ito_f=0.999977
Initial ato_s=4.17069E-4, ito_s=0.998543
Initial nKs=2.62753E-4, aur=4.17069E-4, iur=0.998543
Initial aKss=4.17069E-4, iKss=1.0
Initial C_K1=9.92513E-4, C_K2=6.41229E-4
Initial O_K=1.75298E-4, I_K=3.19129E-5
Initial Cass=0.115001, CaJSR=1299.5, CaNSR=1299.5
Initial P_RyR=0.0
Initial LTRPN_Ca=11.2684, HTRPN_Ca=125.29
Initial O=9.30308E-19, O1=1.49102E-5, O2=9.51726E-11
Initial P_C2=1.6774E-4
Initial C2=1.24216E-4, C3=5.78679E-9, C4=1.19816E-13
Initial I1=4.97023E-19, I2=3.45847E-14, I3=1.85106E-14

# Stimulus protocol
Par r0=1, period=300, pulse=10
Par tf=0, tp=5, tstart=10
ts=t-tstart
rstar = r0 + pulse*(heav(mod(ts,period)-tf)-heav(mod(ts,period)-(tf+tp)))

Par  Nao=140000.0
Par  LTRPN_tot=70.0
Par  kf=0.023761
Par  kb=0.036778
Par  Km_CSQN=800.0
Par  i_pCa_max=1.0
Par  CMDN_tot=50.0
Par  Kpc_max=0.23324
Par  Km_CMDN=0.238
Par  K_mCa=1380.0
Par  Km_Nai=21.0
Par  v1=4.5, v2=1.7E-5, v3=0.45
Par  k_plus_c=0.0090
Par  k_minus_ltrpn=0.196
Par  g_Cab=3.67E-4
Par  k_plus_b=0.00405
Par  k_plus_a=0.006075
Par  Km_up=0.5
Par  K_mNa=87500.0
Par  Km_Cl=10.0
Par  CSQN_tot=15000.0
Par  k_minus_htrpn	=3.2E-5
Par  Km_pCa=0.5
Par  k_plus_ltrpn=0.0327
Par  Acap=1.534E-4
Par  g_Na=13.0, g_CaL=1.51729, g_Ks=0.000575, g_Kr=0.0078, g_Kur=0.0016
Par  g_ClCa=10.0
Par  Vss=1.485E-9
Par  k_NaCa=992.8
Par  k_plus_htrpn=0.00237
Par  Ko=5400.0, Cao=1800.0
Par  tau_xfer=8.0
Par  k_sat	=0.1
Par  n=4.0
Par  g_Kto_f=0.4067, g_Kto_s=0.01, g_Nab=0.0026
Par  m=3.0
Par  Km_Ko=1.5
Par  g_Kss=0.05
Par  HTRPN_tot=140.0
Par  i_NaK_max=0.88
Par  i_CaL_max=7.0
Par  tau_tr=20.0
Par  k_minus_c=8.0E-4
Par  k_minus_b=0.965
Par  k_minus_a=0.07125
Par  Kpc_half=20.0
Par  eta=0.35
Par  Kpcb=5.0E-4

ass = (1.0 / (1.0 + exp( - (0.12987012987012986 * (22.5 + V)))))
E_K = (ln((Ko / Ki)) * R * Temp / Fara)
i_Ks = (g_Ks * (nKs^2.0) * (V - E_K))
E_Na = (ln((((0.9 * Nao) + (0.1 * Ko)) / ((0.9 * Nai) + (0.1 * Ki)))) * R * Temp / Fara)
i_Kr = (g_Kr * O_K * (V - (ln((((0.98 * Ko) + (0.02 * Nao)) / ((0.98 * Ki) + (0.02 * Nai)))) * R * Temp / Fara)))
i_Kur = (g_Kur * aur * iur * (V - E_K))
sigma = (0.14285714285714285 * (-1.0 + exp((1.4858841010401188E-5 * Nao))))
f_NaK = (1.0 / (1.0 + (0.1245 * exp( - (0.1 * V * Fara / (R * Temp)))) + (0.0365 * sigma * exp( - (Fara * V / (R * Temp))))))
J_leak = (v2 * (CaNSR - Cai))
i_NaCa =	 (k_NaCa * ((exp((eta * V * Fara / (R * Temp))) * (Nai^3.0) * Cao) - (exp(((-1.0 + eta) * V * Fara / (R * Temp))) * (Nao^3.0) * Cai)) / ((K_mNa^3.0) + (Nao^3.0)) / (K_mCa + Cao) / (1.0 + (k_sat * exp(((-1.0 + eta) * V * Fara / (R * Temp))))))
O_ClCa = (0.2 / (1.0 + exp( - (0.12820512820512822 * (-46.7 + V)))))
i_ClCa = (g_ClCa * O_ClCa * (V - E_Cl) * Cai / (Cai + Km_Cl))
i_Nab = (g_Nab * (V - E_Na))
tau_Kss = (13.17 + (39.3 * exp( - (0.0862 * V))))
beta_i1 = (9.5E-4 * exp((0.14285714285714285 * (33.5 + V))) / (1.0 + (0.051335 * exp((0.14285714285714285 * (33.5 + V))))))
beta = (0.05 * exp( - (0.07692307692307693 * (12.0 + V))))
i_Kss = (g_Kss * aKss * iKss * (V - E_K))
i_K1 = (0.2938 * Ko * (V - E_K) / (210.0 + Ko) / (1.0 + exp((0.0896 * (V - E_K)))))
i_NaK = (i_NaK_max * f_NaK * Ko / (1.0 + ((Km_Nai / Nai)^0.66667)) / (Ko + Km_Ko))
J_rel = (v1 * (O1 + O2) * (CaJSR - Cass) * P_RyR)
alpha_n = (4.81333E-6 * (26.5 + V) * (1.0 - exp( - (0.128 * (26.5 + V)))))
alpha_i=	 (0.090821 * exp((0.023391 * (5.0 + V))))
alpha_a =	 (0.18064 * exp((0.03577 * (30.0 + V))))
i_pCa = (i_pCa_max * (Cai^2.0) / ((Km_pCa^2.0) + (Cai^2.0)))
alpha_i1 = (1.52E-4 * exp( - (0.14285714285714285 * (13.5 + V))) / (1.0 + (0.0067083 * exp( - (0.14285714285714285 * (33.5 + V))))))
# i_stim =  - (10.0 * (t > 10.0) * (t < 15.0))
beta_Na13 = (0.22 * exp( - (0.04926108374384236 * (-7.5 + V))))
beta_Na12 =  (0.2 * exp( - (0.04926108374384236 * (-2.5 + V))))
beta_Na11 = (0.1917 * exp( - (0.04926108374384236 * (2.5 + V))))
alpha = (0.4 * exp((0.1 * (12.0 + V))) * (1.0 - (0.75 * exp( - (0.0025 * ((20.0 + V)^2.0)))) + (0.7 * exp( - (0.1 * ((40.0 + V)^2.0))))) / (1.0 + (0.12 * exp((0.1 * (12.0 + V))))))
Bi = ((1.0 + (CMDN_tot * Km_CMDN / ((Km_CMDN + Cai)^2.0)))^(-1.0))
gamma =	 (Kpc_max * Cass / (Kpc_half + Cass))
P_C1= (1.0 - (P_C2 + O1 + O2))
C1= (1.0 - (O + C2 + C2 + C3 + C4 + I1 + I2 + I3))
beta_n= (9.53333E-5 * exp( - (0.038 * (26.5 + V))))
beta_i= (0.006497 * exp( - (0.03268 * (5.0 + V))))
beta_a= (0.3956 * exp( - (0.06237 * (30.0 + V))))
i_Kto_s = (g_Kto_s * ato_s * ito_s * (V - E_K))
i_Kto_f = (g_Kto_f * (ato_f^3.0) * ito_f * (V - E_K))
alpha_Na3 = (7.0E-7 * exp( - (0.12987012987012986 * (7.0 + V))))
beta_Na5 = (0.02 * alpha_Na3)
beta_Na4 = alpha_Na3
beta_Na3 = (0.0084 + (2.0E-5 * (7.0 + V)))
alpha_Na13 = (3.802 / ((0.1027 * exp( - (0.08333333333333333 * (2.5 + V)))) + (0.25 * exp( - (0.006666666666666667 * (2.5 + V))))))
alpha_Na2 = (1.0 / (0.393956 + (0.188495 * exp( - (0.06024096385542168 * (7.0 + V))))))
beta_Na2 = (alpha_Na13 * alpha_Na2 * alpha_Na3 / (beta_Na13 * beta_Na3))
BJSR =	((1.0 + (CSQN_tot * Km_CSQN / ((Km_CSQN + CaJSR)^2.0)))^(-1.0))
tau_iur=	 (1200.0 - (170.0 / (1.0 + exp((0.17543859649122806 * (45.2 + V))))))
E_CaN=	 (ln((Cao / Cai)) * R * Temp / (2.0 * Fara))
i_Cab=	 (g_Cab * (V - E_CaN))
tau_ti_s=	 (270.0 + (1050.0 / (1.0 + exp((0.17543859649122806 * (45.2 + V))))))
Bss=	 ((1.0 + (CMDN_tot * Km_CMDN / ((Km_CMDN + Cass)^2.0)))^(-1.0))
alpha_Na12=	 (3.802 / ((0.1027 * exp( - (0.06666666666666667 * (2.5 + V)))) + (0.23 * exp( - (0.006666666666666667 * (2.5 + V))))))
alpha_Na11=	 (3.802 / ((0.1027 * exp( - (0.058823529411764705 * (2.5 + V)))) + (0.2 * exp( - (0.006666666666666667 * (2.5 + V))))))
tau_aur=	 (2.058 + (0.493 * exp( - (0.0629 * V))))
beta_a1=	 (6.89E-5 * exp( - (0.04178 * V)))

beta_a0=	 (0.047002 * exp( - (0.0631 * V)))
J_xfer=	 ((Cass - Cai) / tau_xfer)
tau_ta_s=	 (2.058 + (0.493 * exp( - (0.0629 * V))))
J_up= (v3 * (Cai^2.0) / ((Km_up^2.0) + (Cai^2.0)))
alpha_Na5 = (1.0526315789473684E-5 * alpha_Na2)
alpha_Na4 = (0.0010 * alpha_Na2)
iss = (1.0 / (1.0 + exp((0.17543859649122806 * (45.2 + V)))))
Kpcf = (13.0 * (1.0 - exp( - (0.01 * ((14.5 + V)^2.0)))))
C_K0 = (1.0 - (C_K1 + C_K2 + O_K + I_K))
J_tr = ((CaNSR - CaJSR) / tau_tr)
alpha_a1= (0.013733 * exp((0.038198 * V)))
alpha_a0 = (0.022348 * exp((0.01176 * V)))
J_trpn = ( - ((k_minus_htrpn * HTRPN_Ca) + (k_minus_ltrpn * LTRPN_Ca)) + (k_plus_htrpn * Cai * (HTRPN_tot - HTRPN_Ca)) + (k_plus_ltrpn * Cai * (LTRPN_tot - LTRPN_Ca)))
C_Na3 = (1.0 - (O_Na + C_Na1 + C_Na2 + IF_Na + I1_Na + I2_Na + IC_Na2 + IC_Na3))

i_Na=	 (g_Na * O_Na * (V - E_Na))
i_CaL=	 (g_CaL * O * (V - E_CaL))

V'= - ((i_CaL + i_pCa + i_NaCa + i_Cab + i_Na + i_Nab + i_NaK + i_Kto_f + i_Kto_s + i_K1 + i_Ks + i_Kur + i_Kss + i_Kr + i_ClCa - rstar) / Cm)
Cai'=(Bi * ( - (J_up + J_trpn + (( - (2.0 * i_NaCa) + i_Cab + i_pCa) * Acap * Cm / (2.0 * Vmyo * Fara))) + J_leak + J_xfer))
Cass'=(Bss * ((J_rel * VJSR / Vss) - ((J_xfer * Vmyo / Vss) + (i_CaL * Acap * Cm / (2.0 * Vss * Fara)))))
CaJSR'=(BJSR * (J_tr - J_rel))
CaNSR'=(((J_up - J_leak) * Vmyo / VNSR) - (J_tr * VJSR / VNSR))
P_RyR'=( - (0.04 * P_RyR) - (0.1 * exp( - (0.0015432098765432098 * ((-5.0 + V)^2.0))) * i_CaL / i_CaL_max))
LTRPN_Ca'=((k_plus_ltrpn * Cai * (LTRPN_tot - LTRPN_Ca)) - (k_minus_ltrpn * LTRPN_Ca))
HTRPN_Ca'=((k_plus_htrpn * Cai * (HTRPN_tot - HTRPN_Ca)) - (k_minus_htrpn * HTRPN_Ca))
O1'=( - ((k_minus_a * O1) + (k_plus_b * (Cass^m) * O1) + (k_plus_c * O1)) + (k_plus_a * (Cass^n) * P_C1) + (k_minus_b * O2) + (k_minus_c * P_C2))
O2'=((k_plus_b * (Cass^m) * O1) - (k_minus_b * O2))
P_C2'=((k_plus_c * O1) - (k_minus_c * P_C2))
O'=( - ((4.0 * beta * O) + (gamma * O)) + (alpha * C4) + (Kpcb * I1) + (0.0010 * ((alpha * I2) - (Kpcf * O))))
C2'=( - ((beta * C2) + (3.0 * alpha * C2)) + (4.0 * alpha * C1) + (2.0 * beta * C3))
C3'=( - ((2.0 * beta * C3) + (2.0 * alpha * C3)) + (3.0 * alpha * C2) + (3.0 * beta * C4))
C4'=( - ((3.0 * beta * C4) + (alpha * C4) + (gamma * Kpcf * C4)) + (2.0 * alpha * C3) + (4.0 * beta * O) + (0.01 * ((4.0 * Kpcb * beta * I1) - (alpha * gamma * C4))) + (0.0020 * ((4.0 * beta * I2) - (Kpcf * C4))) + (4.0 * beta * Kpcb * I3))
I1'=( - (Kpcb * I1) + (gamma * O) + (0.0010 * ((alpha * I3) - (Kpcf * I1))) + (0.01 * ((alpha * gamma * C4) - (4.0 * beta * Kpcf * I1))))
I2'=( - (gamma * I2) + (0.0010 * ((Kpcf * O) - (alpha * I2))) + (Kpcb * I3) + (0.0020 * ((Kpcf * C4) - (4.0 * beta * I2))))
I3'=( - ((4.0 * beta * Kpcb * I3) + (Kpcb * I3)) + (0.0010 * ((Kpcf * I1) - (alpha * I3))) + (gamma * I2) + (gamma * Kpcf * C4))
Nai'= - (Acap * Cm * (i_Na + i_Nab + (3.0 * i_NaK) + (3.0 * i_NaCa)) / (Vmyo * Fara))
C_Na2'=( - ((beta_Na11 * C_Na2) + (alpha_Na12 * C_Na2) + (beta_Na3 * C_Na2)) + (alpha_Na11 * C_Na3) + (beta_Na12 * C_Na1) + (alpha_Na3 * IC_Na2))
C_Na1'=( - ((beta_Na12 * C_Na1) + (alpha_Na13 * C_Na1) + (beta_Na3 * C_Na1)) + (alpha_Na12 * C_Na2) + (beta_Na13 * O_Na) + (alpha_Na3 * IF_Na))
O_Na'=( - ((beta_Na13 * O_Na) + (alpha_Na2 * O_Na)) + (alpha_Na13 * C_Na1) + (beta_Na2 * IF_Na))
IF_Na'=( - ((beta_Na2 * IF_Na) + (alpha_Na3 * IF_Na) + (alpha_Na4 * IF_Na) + (beta_Na12 * IF_Na)) + (alpha_Na2 * O_Na) + (beta_Na3 * C_Na1) + (beta_Na4 * I1_Na) + (alpha_Na12 * IC_Na2))
I1_Na'=( - ((beta_Na4 * I1_Na) + (alpha_Na5 * I1_Na)) + (alpha_Na4 * IF_Na) + (beta_Na5 * I2_Na))
I2_Na'=((alpha_Na5 * I1_Na) - (beta_Na5 * I2_Na))
IC_Na2'=( - ((beta_Na11 * IC_Na2) + (alpha_Na12 * IC_Na2) + (alpha_Na3 * IC_Na2)) + (alpha_Na11 * IC_Na3) + (beta_Na12 * IF_Na) + (beta_Na3 * IC_Na2))
IC_Na3'=( - ((alpha_Na11 * IC_Na3) + (alpha_Na3 * IC_Na3)) + (beta_Na11 * IC_Na2) + (beta_Na3 * C_Na3))
Ki'= - (Acap * Cm * (i_Kto_f + i_Kto_s + i_K1 + i_Ks + i_Kss + i_Kur + i_Kr + (2.0 * i_NaK)) / (Vmyo * Fara))
ato_f'=((alpha_a * (1.0 - ato_f)) - (beta_a * ato_f))
ito_f'=((alpha_i1 * (1.0 - ito_f)) - (beta_i1 * ito_f))
ato_s' = ((ass - ato_s) / tau_ta_s)
ito_s' = ((iss - ito_s) / tau_ti_s)
nKs'=((alpha_n * (1.0 - nKs)) - (beta_n * nKs))
aur'=((ass - aur) / tau_aur)
iur'=((iss - iur) / tau_iur)
aKss'=((ass - aKss) / tau_Kss)
iKss'=0.0
C_K2'=( - ((kb * C_K2) + (alpha_a1 * C_K2)) + (kf * C_K1) + (beta_a1 * O_K))
C_K1'=( - ((beta_a0 * C_K1) + (kf * C_K1)) + (alpha_a0 * C_K0) + (kb * C_K2))
O_K'=( - ((beta_a1 * O_K) + (alpha_i * O_K)) + (alpha_a1 * C_K2) + (beta_i * I_K))
I_K'=((alpha_i * O_K) - (beta_i * I_K))

aux ina=i_Na
aux ical=i_CaL
aux ikur=i_Kur

# Numerical and plotting parameters for xpp
@ maxstor=5000000, bounds=10000000, total=1100, xp=t, yp=V, trans=860
@ meth=Gear, dt=0.05, toler=0.01, xlo=860, xhi=1100, ylo=-100, yhi=60     

done

Loading data, please wait...