# Adoped from Pinsky-Rinzel CA3 pyramidal cell model
# Pinsky and Rinzel, J Comput Neurosci 1994;1:39-60.
# K(ATP) channel was inserted into the model.
# Parameters for K(ATP) channels are from Koyto model
# Matsuoka et al. Prog Biophys Mol Biol 2004;85:279-299.
# Simulation results were mimicked by the data from H19-7 cells.
# Simulation of zonisamide (ZNS) effect on CA3 pyramidal cells
# Implemented by Drs. Sheng-Nan Wu and Chin-Wei Huang

# initial conditions
init Vs=-60 Vd=-60

# Parameter values
par ip0=0.75
par gLs=0.1  gLd=0.1  gKdr=15  gCa=1  gKahp=0.8

# Parameter values: simulate ZNS effect final_gNa=17  final_gKCa=40,
par init_gKCa=20  final_gKCa=40
par init_gNa=18  final_gNa=17
par VNa=60  VCa=80  VK=-75  VL=-60  Vsyn=0
par gc=2.1 pp=0.5  Cm=3
par alphac=2 betac=0.1
par tstim=8.0e3 n=500
par gkatp=0.0236*(4^0.24)
par iatp=0.1
par natp=50
gKC=if(t<tstim)then(init_gKCa)else(final_gKCa)
gNa=if(t<tstim)then(init_gNa)else(final_gNa)

# Output cols are t, ODEs, AUXs in order, here:
# t versus vd cad hs ns sd cd qd gqk gkc 
Vs'=(-gLs*(Vs-VL)-gNa*(Minfs(Vs)^2)*hs*(Vs-VNa)-gKdr*ns*(Vs-VK)-gkatp*natp*poatp*(Vs-VK)+(gc/pp)*(Vd-Vs)+Ip0/pp)/Cm
Vd'=(-gLd*(Vd-VL)-ICad-gKahp*qd*(Vd-VK)-gKC*cd*chid*(Vd-VK)-gkatp*natp*poatp*(Vd-VK)+(gc*(Vs-Vd))/(1.0-pp))/Cm
Cad'=  -0.13*ICad-0.075*Cad
hs'=  alphahs(Vs)-(alphahs(Vs)+betahs(Vs))*hs
ns'=  alphans(Vs)-(alphans(Vs)+betans(Vs))*ns
sd'=  alphasd(Vd)-(alphasd(Vd)+betasd(Vd))*sd
cd'=  alphacd(Vd)-(alphacd(Vd)+betacd(Vd))*cd
qd'=  alphaqd-(alphaqd+betaqd)*qd

# Pyramidal cell functions
ICad =  gCa*sd*sd*(Vd-VCa)
alphams(v) =  0.32*(-46.9-v)/(exp((-46.9-v)/4.0)-1.0)
betams(v) =  0.28*(v+19.9)/(exp((v+19.9)/5.0)-1.0)
Minfs(v) =  alphams(v)/(alphams(v)+betams(v))
alphans(v) =  0.016*(-24.9-v)/(exp((-24.9-v)/5.0)-1.0)
betans(v) =  0.25*exp(-1.0-0.025*v)
alphahs(v) =  0.128*exp((-43.0-v)/18.0)
betahs(v) =  4.0/(1.0+exp((-20.0-v)/5.0))
alphasd(v) = 1.6/(1.0+exp(-0.072*(v-5.0)))
betasd(v) =  0.02*(v+8.9)/(exp((v+8.9)/5.0)-1.0)
alphacd(v) = (1.0-heav(v+10.0))*exp((v+50.0)/11-(v+53.5)/27)/18.975+heav(v+10.0)*2.0*exp((-53.5-v)/27.0)
betacd(v) =  (1.0-heav(v+10.0))*(2.0*exp((-53.5-v)/27.0)-alphacd(v))
alphaqd = min(0.00002*Cad,0.01)
betaqd = 0.001
chid = min(Cad/250.0,1.0)

# Level of intracellular ATP concentration
poatp = 0.8/(1+(iatp/0.023)^2)

# auxiliary equationns
aux Ica=ICad
aux gkq = gKahp*qd
aux ikca = gKC*cd*chid*(Vd-VK)
aux ina = gNa*(Minfs(Vs)^2)*hs*(Vs-VNa)
aux ikatp = gkatp*natp*poatp*(Vs-VK)

# integrator params
@ maxstor=1600000,total=2.0e4,bound=10000,xlo=0,xhi=2.0e4,ylo=-90,yhi=40
@ meth=cvode,atol=0.0001,toler=0.0001,dt=0.05

done