#fridlyand1



#reactions
ATP_Ca_dependent_consumption:
 {1.0}ATP_cyt = $pool
  Cytoplasm * katpca * Ca_cyt * ATP_cyt
ATP_Capump:
 {1.0}ATP_cyt = $pool
  I_CaPump / F
ATP_Jerp:
 {1.0}ATP_cyt = $pool
  Cytoplasm * Jerp / 2
ATP_NaKATPase:
 {1.0}ATP_cyt = $pool
  I_NaK / F
ATP_consumption:
 {1.0}ATP_cyt = $pool
  Cytoplasm * katp * ATP_cyt
ATP_production:
 $pool = {1.0}ATP_cyt
  Cytoplasm * kadp * ADP_cyt
Calcium_cyt_Icapump:
 {1.0}Ca_cyt = $pool
  fi * 2 * I_CaPump / (2 * F)
Calcium_cyt_Inaca:
 $pool = {1.0}Ca_cyt
  fi * 2 * I_NaCa / (2 * F)
Calcium_cyt_Ivca:
 $pool = {1.0}Ca_cyt
  fi * -I_Vca / (2 * F)
Calcium_cyt_Jerp:
 {0.01}Ca_cyt = {0.03}Ca_er
  Cytoplasm * Jerp
Calcium_cyt_Jout:
 {0.03}Ca_er = {0.01}Ca_cyt
  Jout
Calcium_cyt_sequestration:
 {1.0}Ca_cyt = $pool
  Cytoplasm * ksg * Ca_cyt
IP3_degradation:
 {1.0}IP3_cyt = $pool
  Cytoplasm * kdip * IP3_cyt
IP3_synthesis:
 $pool = {1.0}IP3_cyt
  Cytoplasm * kip * pow(Ca_cyt, 2) / (pow(Ca_cyt, 2) + pow(Kipca, 2))
Na_Icran:
 $pool = {1.0}Na_cyt
  -I_CRAN / F
Na_Ina:
 $pool = {1.0}Na_cyt
  -I_Na / F
Na_Inaca:
 {1.0}Na_cyt = $pool
  3 * I_NaCa / F
Na_Inak:
 {1.0}Na_cyt = $pool
  3 * I_NaK / F


#parameters
Ca_ec = 2600.0
Cm = 6158.0
F = 9.6485e+16
K_cyt = 132400.0
K_ec = 8000.0
Kcah = 9.5
Kcap = 0.1
Kcar = 200.0
Kcarp = 0.5
Kdd = 17.0
Kip3 = 3.2
Kipca = 0.4
Kkca = 0.1
Knaca = 0.75
Krca = 0.077
Ksup = 150400.0
Ktd = 26.0
Ktt = 1.0
Na_ec = 140000.0
P = 4950.0
Pcaer = 0.105
Pip3 = 1.2e-15
Pleak = 1e-16
Pmcap = 2000.0
Pnak = 600.0
Sn = 7.0
TV = 26.73
V_CRAN = 0.0
Vcah = -19.0
Vn = -14.0
Vtau = -75.0
a = 65.0
b = 20.0
b5_ast = 0.03
b_1 = 100.0
b_2 = 0.0001
b_3 = 1.72e-17
b_4 = 0.0002
b_6 = 6e-07
c = 20.0
f5_ast = 0.002
f_1 = 2.5e-10
f_2 = 10.0
f_3 = 0.172
f_4 = 1.5e-08
f_6 = 11.5
fer = 0.03
fi = 0.01
gmKDr = 3000.0
gm_CRAN = 0.7
gmkatp = 24000.0
gmkca = 130.0
gmna = 1200.0
gmvca = 770.0
gnaca = 271.0
kadp = 0.00037
katp = 5e-05
katpca = 5e-05
kdip = 4e-05
kip = 0.0003
ksg = 0.0001
Cytoplasm = 7.64e-13
ER = 2.8e-13


#initial values
ATP_cyt = 932.1
Ca_cyt = 0.085
Ca_er = 22.8
IP3_cyt = 0.33
Na_cyt = 9858.0
V = -60.9
n = 0.00123


#assignment rules
!F ADP_cyt = 4000.0 - ATP_cyt
!F Vca = TV / 2.0 * log(Ca_ec / Ca_cyt)
!F Vk = TV * log(K_ec / K_cyt)
!F Vna = TV * log(Na_ec / Na_cyt)
!F pvca = 1.0 / (1.0 + exp((Vcah - V) / Kcah))
!F p_CRAN = V - V_CRAN
!F I_CaPump = Pmcap * pow(Ca_cyt, 2.0) / (pow(Kcap, 2.0) + pow(Ca_cyt, 2.0))
!F f_5 = f5_ast * exp(V / (2.0 * TV))
!F b_5 = b5_ast * exp(-V / (2.0 * TV))
!F I_Vca = gmvca * 1.0 / (1.0 + exp((Vcah - V) / Kcah)) * (V - TV / 2.0 * log(Ca_ec / Ca_cyt))
!F Jout = (Pleak + Pip3 * O_infinity) * (Ca_er - Ca_cyt)
!F B2 = b_2 * (4000.0 - ATP_cyt)
!F B3 = b_3 * pow(Na_ec, 3.0)
!F B4 = b_4 * P
!F f_Ca = pow(Ca_cyt, 4.0) / (pow(Ca_cyt, 4.0) + pow(Kkca, 4.0))
!F B6 = b_6 * pow(Ksup, 2.0)
!F tau_n = c / (exp((V - Vtau) / a) + exp((Vtau - V) / b))
!F F5 = (f5_ast * exp(V / (2.0 * TV))) * ATP_cyt
!F n_infinity = 1.0 / (1.0 + exp((Vn - V) / Sn))
!F F4 = f_4 * pow(K_ec, 2.0)
!F Jerp = Pcaer * pow(Ca_cyt, 2.0) / (pow(Ca_cyt, 2.0) + pow(Kcarp, 2.0))
!F I_KDr = gmKDr * n * (V - (TV * log(K_ec / K_cyt)))
!F I_Na = gmna * (1.0 / (1.0 + exp((104.0 + V) / 8.0))) * (V - TV * log(Na_ec / Na_cyt))
!F I_NaK = Pnak * (f_1 * pow(Na_cyt, 3.0) * f_2 * f_3 * (f_4 * pow(K_ec, 2.0)) * ((f5_ast * exp(V / (2.0 * TV))) * ATP_cyt) * f_6 - b_1 * (b_2 * (4000.0 - ATP_cyt)) * (b_3 * pow(Na_ec, 3.0)) * (b_4 * P) * b5_ast * exp(-V / (2.0 * TV)) * b_6 * pow(Ksup, 2.0)) / D
!F D = f_2 * f_3 * f_4 * pow(K_ec, 2.0) * (f5_ast * exp(V / (2.0 * TV))) * ATP_cyt * f_6 + b_1 * f_3 * f_4 * pow(K_ec, 2.0) * (f5_ast * exp(V / (2.0 * TV))) * ATP_cyt * f_6 + b_1 * b_2 * (4000.0 - ATP_cyt) * f_4 * pow(K_ec, 2.0) * (f5_ast * exp(V / (2.0 * TV))) * ATP_cyt * f_6 + b_1 * b_2 * (4000.0 - ATP_cyt) * b_3 * pow(Na_ec, 3.0) * (f5_ast * exp(V / (2.0 * TV))) * ATP_cyt * f_6 + b_1 * b_2 * (4000.0 - ATP_cyt) * b_3 * pow(Na_ec, 3.0) * b_4 * P * f_6 + b_1 * b_2 * (4000.0 - ATP_cyt) * b_3 * pow(Na_ec, 3.0) * b_4 * P * b5_ast * exp(-V / (2.0 * TV))
!F I_KATP = gmkatp * ((0.08 * (1.0 + 0.33 * ((4000.0 - ATP_cyt) / Kdd)) + 0.89 * pow(0.165 * ((4000.0 - ATP_cyt) / Kdd), 2.0)) / (pow(1.0 + 0.165 * ((4000.0 - ATP_cyt) / Kdd), 2.0) * (1.0 + 0.135 * ((4000.0 - ATP_cyt) / Ktd) + 0.05 * (ATP_cyt / Ktt)))) * (V - (TV * log(K_ec / K_cyt)))
!F O_infinity = Ca_cyt * pow(IP3_cyt, 3.0) / ((Ca_cyt + Krca) * (pow(IP3_cyt, 3.0) + pow(Kip3, 3.0)))
!F I_KCa = gmkca * (pow(Ca_cyt, 4.0) / (pow(Ca_cyt, 4.0) + pow(Kkca, 4.0))) * (V - (TV * log(K_ec / K_cyt)))
!F I_CRAN = (-gm_CRAN / (1.0 + exp((Ca_er - Kcar) / 3.0))) * (V - V_CRAN) * (V - TV * log(Na_ec / Na_cyt))
!F I_NaCa = gnaca * pow(Ca_cyt, 5.0) * (V - (TV * (3.0 * log(Na_ec / Na_cyt) - log(Ca_ec / Ca_cyt)))) / (pow(Ca_cyt, 5.0) + pow(Knaca, 5.0))
!F Okatp = (0.08 * (1.0 + 0.33 * ((4000.0 - ATP_cyt) / Kdd)) + 0.89 * pow(0.165 * ((4000.0 - ATP_cyt) / Kdd), 2.0)) / (pow(1.0 + 0.165 * ((4000.0 - ATP_cyt) / Kdd), 2.0) * (1.0 + 0.135 * ((4000.0 - ATP_cyt) / Ktd) + 0.05 * (ATP_cyt / Ktt)))
!F F1 = f_1 * pow(Na_cyt, 3.0)
!F pna = 1.0 / (1.0 + exp((104.0 + V) / 8.0))
!F f_CRAN = -gm_CRAN / (1.0 + exp((Ca_er - Kcar) / 3.0))
!F Vnaca = TV * (3.0 * log(Na_ec / Na_cyt) - log(Ca_ec / Ca_cyt))