: Calcium ion accumulation with radial and longitudinal diffusion and pump
NEURON {
SUFFIX cdpAIS
USEION ca READ cao, cai, ica WRITE cai
RANGE ica_pmp,ca1,ca2,ca3,ca4,ca5,ca9
:RANGE pump_0
GLOBAL vrat, TotalPump
: vrat must be GLOBAL--see INITIAL block
: however TotalBuffer and TotalPump may be RANGE
: THREADSAFE
}
DEFINE Nannuli 10
UNITS {
(mol) = (1)
(molar) = (1/liter)
(mM) = (millimolar)
(um) = (micron)
(mA) = (milliamp)
FARADAY = (faraday) (10000 coulomb)
PI = (pi) (1)
}
PARAMETER {
v
celsius =34 (degC)
:cainull =2.5e-4 (mM)
cainull = 45e-6 (mM)
mginull =.59 (mM)
DCa = .233 (um2/ms)
Dbtc = 0.007 (um2/ms)
Ddmnpe = 0.08 (um2/ms)
Dcbd1 = .028 (um2/ms)
Dcbd2 = 0 (um2/ms)
Dpar = .043 (um2/ms)
: values for benzothiazole coumarin (BTC)
: BTCnull = 0 (mM)
: b1 = 5.33 (/ms mM)
: b2 = 0.08 (/ms)
: values for caged compound DMNPE-4
: DMNPEnull = 0 (mM)
: c1 = 5.63 (/ms mM)
: c2 = 0.107e-3 (/ms)
: values for Calbindin (2 high and 2 low affinity binding sites)
: CBnull= .16 (mM)
CBnull= .08 (mM)
nf1 =43.5 (/ms mM)
nf2 =3.58e-2 (/ms)
ns1 =5.5 (/ms mM)
ns2 =0.26e-2 (/ms)
: values for Parvalbumin
: PVnull = 0.08 (mM)
PVnull = 0.04 (mM)
m1 = 1.07e2 (/ms mM)
m2 = 9.5e-4 (/ms)
p1 = 0.8 (/ms mM)
p2 = 2.5e-2 (/ms)
kpmp1 = 3e3 (/mM-ms)
kpmp2 = 1.75e1 (/ms)
kpmp3 = 7.255e1 (/ms)
: to eliminate pump, set TotalPump to 0 in hoc
TotalPump = 1e-15
: TotalPump = 1e-8
beta = 1(1) :introducing beta to take care of other ER mechanisms(SERCA and leak channel density)
vmax =0.1
:Kp = 0.27e-3 (mM)
Kp = 2.7e-3 (mM)
}
ASSIGNED {
diam (um)
ica (mA/cm2)
ica_pmp (mA/cm2)
ibg :background calcium current
: ica_pmp_last (mA/cm2)
parea (um) : pump area per unit length
cai (mM)
ca1
ca2
ca3
ca4
ca5
ca9
mgi (mM)
vrat[Nannuli] (1) : dimensionless
: numeric value of vrat[i] equals the volume
: of annulus i of a 1um diameter cylinder
: multiply by diam^2 to get volume per um length
}
CONSTANT { cao = 2 (mM) }
STATE {
: ca[0] is equivalent to cai
: ca[] are very small, so specify absolute tolerance
: let it be ~1.5 - 2 orders of magnitude smaller than baseline level
ca[Nannuli] (mM)
mg[Nannuli] (mM) <1e-7>
CB[Nannuli] (mM)
CB_f_ca[Nannuli] (mM)
CB_ca_s[Nannuli] (mM)
CB_ca_ca[Nannuli] (mM)
iCB[Nannuli] (mM)
iCB_f_ca[Nannuli] (mM)
iCB_ca_s[Nannuli] (mM)
iCB_ca_ca[Nannuli] (mM)
PV[Nannuli] (mM)
PV_ca[Nannuli] (mM)
PV_mg[Nannuli] (mM)
pump (mol/cm2) <1e-15>
pumpca (mol/cm2) <1e-15>
}
BREAKPOINT {
SOLVE state METHOD sparse
: ica_pmp_last = ica_pmp
: ica = ica_pmp
}
LOCAL factors_done
INITIAL {
if (factors_done == 0) { : flag becomes 1 in the first segment
factors_done = 1 : all subsequent segments will have
factors() : vrat = 0 unless vrat is GLOBAL
}
FROM i=0 TO Nannuli-1 {
ca[i] = cainull
mg[i] = mginull
CB[i] = 0.8*ssCB( kdf(), kds())
CB_f_ca[i] = 0.8*ssCBfast( kdf(), kds())
CB_ca_s[i] = 0.8*ssCBslow( kdf(), kds())
CB_ca_ca[i] = 0.8*ssCBca( kdf(), kds())
iCB[i] = 0.2*ssCB( kdf(), kds())
iCB_f_ca[i] = 0.2*ssCBfast( kdf(), kds())
iCB_ca_s[i] = 0.2*ssCBslow( kdf(), kds())
iCB_ca_ca[i] = 0.2*ssCBca(kdf(), kds())
PV[i] = ssPV( kdc(), kdm())
PV_ca[i] = ssPVca(kdc(), kdm())
PV_mg[i] = ssPVmg(kdc(), kdm())
}
parea = PI*diam
ica = 0
ica_pmp = 0
: ica_pmp_last = 0
pump = TotalPump
pumpca = 0
}
LOCAL frat[Nannuli] : scales the rate constants for model geometry
PROCEDURE factors() {
LOCAL r, dr2
r = 1/2 : starts at edge (half diam)
dr2 = r/(Nannuli-1)/2 : full thickness of outermost annulus,
: half thickness of all other annuli
vrat[0] = 0
frat[0] = 2*r
FROM i=0 TO Nannuli-2 {
vrat[i] = vrat[i] + PI*(r-dr2/2)*2*dr2 : interior half
r = r - dr2
frat[i+1] = 2*PI*r/(2*dr2) : outer radius of annulus
: div by distance between centers
r = r - dr2
vrat[i+1] = PI*(r+dr2/2)*2*dr2 : outer half of annulus
}
}
LOCAL dsq, dsqvol : can't define local variable in KINETIC block
: or use in COMPARTMENT statement
KINETIC state {
COMPARTMENT i, diam*diam*vrat[i] {ca mg CB CB_f_ca CB_ca_s CB_ca_ca iCB iCB_f_ca iCB_ca_s iCB_ca_ca PV PV_ca PV_mg}
COMPARTMENT (1e10)*parea {pump pumpca}
:pump
: ~ ca[0] + pump <-> pumpca (kpmp1*parea*(1e10), kpmp2*parea*(1e10))
: ~ pumpca <-> pump (kpmp3*parea*(1e10), 0)
: CONSERVE pump + pumpca = TotalPump * parea * (1e10)
: ica_pmp = 2*FARADAY*(f_flux - b_flux)/parea
: all currents except pump
: ica is Ca efflux
~ ca[0] << (-ica*PI*diam/(2*FARADAY))
:RADIAL DIFFUSION OF ca, mg and mobile buffers
FROM i=0 TO Nannuli-1 {
~ ca[i] << (-beta*vmax*vrat[i]*ca[i] / (ca[i] + kpmp2/kpmp1))
}
FROM i=0 TO Nannuli-2 {
~ ca[i] <-> ca[i+1] (DCa*frat[i+1], DCa*frat[i+1])
~ mg[i] <-> mg[i+1] (DCa*frat[i+1], DCa*frat[i+1])
~ CB[i] <-> CB[i+1] (Dcbd1*frat[i+1], Dcbd1*frat[i+1])
~ CB_f_ca[i] <-> CB_f_ca[i+1] (Dcbd1*frat[i+1], Dcbd1*frat[i+1])
~ CB_ca_s[i] <-> CB_ca_s[i+1] (Dcbd1*frat[i+1], Dcbd1*frat[i+1])
~ CB_ca_ca[i] <-> CB_ca_ca[i+1] (Dcbd1*frat[i+1], Dcbd1*frat[i+1])
~ PV[i] <-> PV[i+1] (Dpar*frat[i+1], Dpar*frat[i+1])
~ PV_ca[i] <-> PV_ca[i+1] (Dpar*frat[i+1], Dpar*frat[i+1])
~ PV_mg[i] <-> PV_mg[i+1] (Dpar*frat[i+1], Dpar*frat[i+1])
}
dsq = diam*diam
FROM i=0 TO Nannuli-1 {
dsqvol = dsq*vrat[i]
:Calbindin
~ ca[i] + CB[i] <-> CB_ca_s[i] (nf1*dsqvol, nf2*dsqvol)
~ ca[i] + CB[i] <-> CB_f_ca[i] (ns1*dsqvol, ns2*dsqvol)
~ ca[i] + CB_f_ca[i] <-> CB_ca_ca[i] (nf1*dsqvol, nf2*dsqvol)
~ ca[i] + CB_ca_s[i] <-> CB_ca_ca[i] (ns1*dsqvol, ns2*dsqvol)
~ ca[i] + iCB[i] <-> iCB_ca_s[i] (nf1*dsqvol, nf2*dsqvol)
~ ca[i] + iCB[i] <-> iCB_f_ca[i] (ns1*dsqvol, ns2*dsqvol)
~ ca[i] + iCB_f_ca[i] <-> iCB_ca_ca[i] (nf1*dsqvol, nf2*dsqvol)
~ ca[i] + iCB_ca_s[i] <-> iCB_ca_ca[i] (ns1*dsqvol, ns2*dsqvol)
:Paravalbumin
~ ca[i] + PV[i] <-> PV_ca[i] (m1*dsqvol, m2*dsqvol)
~ mg[i] + PV[i] <-> PV_mg[i] (p1*dsqvol, p2*dsqvol)
}
cai = ca[0]
ca1 = ca[1]
ca2 = ca[2]
ca3 = ca[3]
ca4 = ca[4]
ca5 = ca[5]
ca9 = ca[9]
: if (ca[0]<cainull){: keep minimum
: cai=cainull }
mgi = mg[0]
}
FUNCTION ssCB( kdf(), kds()) (mM) {
ssCB = CBnull/(1+kdf()+kds()+(kdf()*kds()))
}
FUNCTION ssCBfast( kdf(), kds()) (mM) {
ssCBfast = (CBnull*kds())/(1+kdf()+kds()+(kdf()*kds()))
}
FUNCTION ssCBslow( kdf(), kds()) (mM) {
ssCBslow = (CBnull*kdf())/(1+kdf()+kds()+(kdf()*kds()))
}
FUNCTION ssCBca(kdf(), kds()) (mM) {
ssCBca = (CBnull*kdf()*kds())/(1+kdf()+kds()+(kdf()*kds()))
}
FUNCTION kdf() (1) {
kdf = (cainull*nf1)/nf2
}
FUNCTION kds() (1) {
kds = (cainull*ns1)/ns2
}
FUNCTION kdc() (1) {
kdc = (cainull*m1)/m2
}
FUNCTION kdm() (1) {
kdm = (mginull*p1)/p2
}
FUNCTION ssPV( kdc(), kdm()) (mM) {
ssPV = PVnull/(1+kdc()+kdm())
}
FUNCTION ssPVca( kdc(), kdm()) (mM) {
ssPVca = (PVnull*kdc)/(1+kdc+kdm)
}
FUNCTION ssPVmg( kdc(), kdm()) (mM) {
ssPVmg = (PVnull*kdm())/(1+kdc()+kdm())
}
FUNCTION u (x, th) {
if (x<th) {
u = 1
} else {
u = 0
}
}