# CIPN equations with Paclitaxel affecting the conductances according to the Hill's equation

dv/dt=kt*((I/A)-gNa17f*m17^3*h17*s17*(v-vna)-gNa18f*m18*h18*(v-vna)-gKf*n*(v-vk)-gKAf*nKA*hKA*(v-vk)-gl*(v-vl))/c

dm17/dt=kt*(minf17(v)-m17)/taum17(v)
dh17/dt=kt*(hinf17(v)-h17)/tauh17(v)
ds17/dt=kt*(sinf17(v)-s17)/taus17(v)

dm18/dt=kt*(minf18(v)-m18)/taum18(v)
dh18/dt=kt*(hinf18(v)-h18)/tauh18(v)

dn/dt=kt*(ninf(v)-n)/taun(v)

dnKA/dt=kt*(ninfKA(v)-nKA)/taunKA(v)
dhKA/dt=kt*(hinfKA(v)-hKA)/tauhKA(v)

#Function for Pax effect on g

gNa17f=gNa17+(gNamax-gNa17)*(p^hn/(p^hn+ec50^hn))
gNa18f=gNa18+(gNamax-gNa18)*(p^hn/(p^hn+ec50^hn))
gKf=gK+(gKmin-gK)*(p^hn/(p^hn+ec50^hn))
gKAf=gKA+(gKmin-gKA)*(p^hn/(p^hn+ec50^hn))

#Functions for Nav1.7

am17(v)=15.5/(1+exp(-(v-5)/12.08))
bm17(v)=35.2/(1+exp((v+72.7)/16.7))
taum17(v)=1/(am17(v)+bm17(v))
minf17(v)=taum17(v)*am17(v)

ah17(v)=0.38685/(1+exp((v+122.35)/15.29))
bh17(v)=-0.00283+2.00283/(1+exp(-(v+5.5266)/12.70195))
tauh17(v)=1/(ah17(v)+bh17(v))
hinf17(v)=tauh17(v)*ah17(v)

as17(v)=0.00003+0.00092/(1+exp((v+93.9)/16.6))
bs17(v)=132.05-132.05/(1+exp((v-384.9)/28.5))
taus17(v)=1/(as17(v)+bs17(v))
sinf17(v)=taus17(v)*as17(v)

#Functions for Nav1.8

am18(v)=2.85-(2.839/(1+exp((v-1.159)/13.95)))
bm18(v)=7.6205/(1+exp((v+46.463)/8.8289))
taum18(v)=1/(am18(v)+bm18(v))
minf18(v)=taum18(v)*am18(v)

tauh18(v)=1.218+42.043*exp(-((v+38.1)^2)/(2*15.19^2))
hinf18(v)=1/(1+exp((v+32.2)/4))

#Functions for Kv

an(v)=if(-v!=14.273)then(0.001265*(v+14.273)/(1-exp(-(v+14.273)/10)))else(0.001265*10)
bn(v)=0.125*exp(-(v+55)/2.5)
taun(v)=1/(an(v)+bn(v))+1
ninf(v)=1/(1+exp(-(v+14.62)/18.38))

#Functions for KA
ninfKA(v)=(1/(1+exp(-(v+5.4)/16.4)))^4
taunKA(v)=0.25+10.04*exp(-(v+24.67)^2/(2*34.8^2))
hinfKA(v)=1/(1+exp((v+49.9)/4.6))
tauhKA1(v)=20+50*exp(-(v+40)^2/(2*40^2))
tauhKA(v)=if(tauhKA1(v)<5)then(5)else(tauhKA1(v))

#Parameters
param p=0,I=0,gNa18=7,gNa17=18,gK=4.78,gKA=8.33,gl=0.0575
param c=0.93,A=21.68,kt=1
param vna=67.1,vk=-84.7,vl=-58.91
param hn=1,gNamax=100,gKmin=0.1,ec50=500

#Initial values
#Following initial values are for gNa18=7
init v=-66.47794383085288,m17=0.0028910068679934894,h17=0.4188697707074979,s17=0.9105854454115576,m18=0.004768537866039612,h18=0.9998102258258676,n=0.05617689078937599,nKA=3.082247500291692e-07,hKA=0.9735038111180977

#Options
@ TOTAL=1000,@ NPLOT=1,@ NTST=100,@ PARMAX=5000,@ METH=stiff,@ TOLER=1e-7
done