A model for recurrent spreading depolarizations (Conte et al. 2017)

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Accession:235377
A detailed biophysical model for a neuron/astrocyte network is developed in order to explore mechanisms responsible for cortical spreading depolarizations. This includes a model for the Na+-glutamate transporter, which allows for a detailed description of reverse glutamate uptake. In particular, we consider the specific roles of elevated extracellular glutamate and K+ in the initiation, propagation and recurrence of spreading depolarizations.
Reference:
1 . Conte C, Lee R, Sarkar M, Terman D (2018) A mathematical model of recurrent spreading depolarizations. J Comput Neurosci 44:203-217 [PubMed]
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Model Information (Click on a link to find other models with that property)
Model Type: Extracellular; Glia; Neuron or other electrically excitable cell;
Brain Region(s)/Organism:
Cell Type(s): Astrocyte;
Channel(s): I K; I Na,p; I Cl, leak; Na/K pump; Na+-glutamate transporter;
Gap Junctions:
Receptor(s): Glutamate;
Gene(s):
Transmitter(s): Glutamate;
Simulation Environment: XPP;
Model Concept(s): Detailed Neuronal Models; Potassium buffering; Spreading depression; Spreading depolarization;
Implementer(s): Terman, David [terman at math.ohio-state.edu];
Search NeuronDB for information about:  Glutamate; I Na,p; I K; Na/K pump; I Cl, leak; Na+-glutamate transporter; Glutamate;
######   A mathematical model for recurrent spreading depolarizations
######	 C. Conte, R. Lee, M. Sarkar, D. Terman
######   Journal of Computational Neuroscience

# Gas constant, temperature, Faraday's constant
p R=8310
p Temp=310.0
p F=96485
frt=R*Temp/F
phi(v)=v/frt

###################################################
######  Neurons
###################################################

#########
# Currents
#########

# Fast Na
P pna=1e-05
p pnal=2e-09
p thm=-34.,sigm=5.
minf(v)=1./(1.+exp(-(v-thm)/sigm))
ina(v,n,nae,nai)=PNa*(minf(v)^3*(1-n)+pnal)*F*phi(v)*(Nae*exp(-phi(v))-Nai)/(exp(-phi(v))-1)

# NaP
p pnap=3e-08
p taubar=10000
p thmp=-40,sigmp=6
p thhp=-48,sighp=-6
p vt=-49,sig=6
p phihp=.05
minfp(v)=1./(1.+exp(-(v-thmp)/sigmp))
hinfp(v)=1./(1.+exp(-(v-thhp)/sighp))
tauhp(v)=taubar/cosh((v-vt)/(2*sig))
inap(v,hp,nae,nai)=PNap*minfp(v)*hp*F*phi(v)*(Nae*exp(-phi(v))-Nai)/(exp(-phi(v))-1)

# IK
p pk=7e-05
p pkl=4e-07
p thn=-55.,sgn=14.
p taun0=.05,taun1=.27,thnt=-40,sn=-12
p phin=.8
ninf(v)=1./(1.+exp(-(v-thn)/sgn))
taun(v)=taun0+taun1/(1+exp(-(v-thnt)/sn))
ik(v,n,ke,ki)=PK*(n^4+pkl)*F*phi(v)*(ke*exp(-phi(v))-ki)/(exp(-phi(v))-1)

# NMDA
p pnmda=3e-06
p thetat=-10,trise=2,tdecay=1,alphag=.5
binf(v)=1/(1+exp(-(v-thetat)/16.13))
p pca=3
p thg=.01,sigmag=.001
sinfg(x)=1./(1.+exp(-(x-thg)/sigmag))
inanmda=Pnmda*sg*binf(v)*F*phi(v)*(Nae*exp(-phi(v))-Nai)/(exp(-phi(v))-1)
iknmda=Pnmda*sg*binf(v)*F*phi(v)*(ke*exp(-phi(v))-ki)/(exp(-phi(v))-1)
icanmda=pca*2*Pnmda*sg*binf(v)*F*phi(2*v)*(cae*exp(-phi(2*v))-cai)/(exp(-phi(2*v))-1)
inmda=inanmda+iknmda+icanmda

# Cl leak
p pcl=2e-07
icl(v,cle,cli)=-Pcl*F*phi(-v)*(cle*exp(-phi(-v))-cli)/(exp(-phi(-v))-1)

# Neuron Na-K ATPase pump
p imax=5
ipump=imax/(((1+2/ke)^2)*(1+7.7/nai)^3)
inapump=3*ipump
ikpump=-2*ipump

#########
# Differential equations
#########

v'= -(ina(v,n,nae,nai)+inap(v,hp,nae,nai)+ik(v,n,ke,ki)+icl(v,cle,cli)+ipump+inmda)
n'= phin*(ninf(v)-n)/taun(v)
hp'=phihp*(hinfp(v)-hp)/tauhp(v)
sg'=-sg/tdecay+alphag*sinfg(glut)*(1-sg)


###################################################
######  Astrocytes
###################################################

#########
# Currents
#########

p pka=4.8e-06
ika(v,ke,ki)=PKa*F*phi(v)*(ke*exp(-phi(v))-ki)/(exp(-phi(v))-1)

p pnaa=.015e-06
inaa(v,nae,nai)=PNaa*F*phi(v)*(Nae*exp(-phi(v))-Nai)/(exp(-phi(v))-1)

p eps=.00003
p imin=.08
imaxa'=eps*(imin-imaxa)
i imaxa=5
ipumpa(ke,nai)=imaxa/(((1+2/ke)^2)*(1+10/nai)^3)

# Na-glut co-transporter (in astrocyte)
p hr=.5
p gnagl=3e-05
enagl=(frt/2)*ln(((nae/naia)^3)*(kia/ke)*(glut/glui)*hr)
inagl=gnagl*(va-enagl)

#########
# Differential equation
#########
va'=-(ika(va,ke,kia)+inaa(va,nae,naia)+ipumpa(ke,naia)+inagl)

###################################################
######  Ion concentrations
###################################################

# Volume (um^3) and Area (um^2) of neuron
p voln=2160
p s=922

# Volume and Area of astrocyte
p Sa=1600
p vola=2000 

# Volume of extracellular space
p alpha0=.05
vole=alpha0*voln

# Conversion factors from uA/cm^2 to mM/ms
cfn=10.0*s/(F*voln)
cfne=10.0*s/(F*vole)
cfa=10*sa/(F*vola)
cfae=10*sa/(F*vole)

# Na+, K+ & Cl-

ki'=-cfn*(ik(v,n,ke,ki)+ikpump+iknmda)
ke'=cfne*(ik(v,n,ke,ki)+ikpump+iknmda)+cfae*(ika(va,ke,kia)-2*ipumpa(ke,naia)-inagl)+gkb*(k0-ke)
nai'=-cfn*(ina(v,n,nae,nai)+inap(v,hp,nae,nai)+inapump+inanmda)
nae'=cfne*(ina(v,n,nae,nai)+inap(v,hp,nae,nai)+inapump+inanmda)+cfae*(inaa(va,nae,naia)+3*ipumpa(ke,naia)+(3)*inagl)+gnab*(na0-nae)
kia'=-cfa*(ika(va,ke,kia)-2*ipumpa(ke,naia)-inagl)
naia'=-cfa*(inaa(va,nae,naia)+3*ipumpa(ke,naia)+(3)*inagl)

cli'=cfn*icl(v,cle,cli)
cle'=-cfne*icl(v,cle,cli)+gclb*(cl0-cle)

p gnab=1e-05,gkb=2e-05,gclb=6e-06
p na0=140,k0=4,cl0=110

# Glutamate

glut'=cfae*inagl
gltot=cfae*glui0+cfa*glut0
p glui0=1, glut0=.001
glui=(1/cfae)*(gltot-cfa*glut)


# Ca2+
cai'=-fi*cfn*(icanmda)-fi*(per*der*(jserca-jerout))/(pcytosol*minute*second)
caer'=fi*(per*der*(jserca-jerout))/(per*minute*second)
cae'=cfne*icanmda+gcab*(cae0-cae)
her'=(dinh-(cai+dinh)*her)/tau

jerout=(vip3*((ip3/(ip3+dip3))^3)*((cai/(cai+dact))^3)*(her^3)+vleak)*(caer-cai)
jserca=vserca*cai^2/(kserca^2+cai^2)

p minute=60
p second=1000
p ip3=.3
p pcytosol=0.5
p dcytosol=75
p per=0.10
p der=1000
p fi=.01
p vip3=3000
p vleak=0.01
p dip3=0.25
p dinh=.5
p dact=1
p tau=4
p vserca=110
p kserca=0.4
p gcab=6e-06
p cae0=3


###################################################
######  Initial conditions
###################################################

i v=-80
i n=0.144
i hp=0.995
i sg=0.
i va=-76
i kia=132
i naia=6.2

i ke=7
i nai=1.75
i nae=134
i ki=142
i cli=5.824
i cle=111.26
i glut=.0001

i cae=3
i cai=.001
i her=0.99
i caer=.057

### XPP settings

@ dt=.5,total=50000,meth=qualrk,tolerance=.0000001
@ xp=t,yp=v,xlo=0,xhi=50000,ylo=-80,yhi=0.,bound=500000,maxstor=1000000

done