COMMENT
This file, ca_soma.mod, for Quadroni and Knopfel 1994, was modified from
the cylindrical diffusion model cadifus.mod from Chapter 9 Hines and Carnevale NEURON
This file is different than the other ca_[dist|prox].mod files in that it models spherical
shell diffusion rather than cylindrical shells.
ENDCOMMENT
: Calcium ion accumulation with radial diffusion in shells
NEURON {
SUFFIX ca_soma
USEION ca READ cai, ica WRITE cai
NONSPECIFIC_CURRENT ifake : used to move the calc. of the breakpt. to same t as other currents
GLOBAL vrat : vrat must be GLOBAL --see INITIAL block
: however B which in cadifus.mod was called TotalBuffer may be and is here RANGE
GLOBAL factor : diagnostic variable for concentration dependent studies
RANGE K2f_ex, K2f_ATPase, B : Note capital K2f_'s are intensive qty's, i.e. (mA/cm2 mM4)
RANGE i_Na_Ca_ex, i_ATPase, I : I is used to display ica_ values for this mechanism
: Na Ca exchanger can pump one Ca out for 3 Na's
: that enter the cell.
: the ATPase current pumps Ca out of the cell by
: using up ATP
}
DEFINE Nthin 5 : Nthin = # of thin spherical shells that are all within and take up
: the outermost thick shell. The thick shells are evenly distributed
: throughout the sphere in this first model. A future version closer
: to the paper will model the distribution with each thick shell having
: constant volume
DEFINE Nthick 21 : # of thick spherical shells including the last one which is divided by above
DEFINE Nshells 25 : ((Nthick-1) + Nthin) : total number of shells
UNITS {
(molar) = (1/liter)
(mM) = (millimolar)
(um) = (micron)
(mA) = (milliamp)
(mV) = (millivolt)
FARADAY = (faraday) (10000 coulomb)
PI = (pi) (1)
}
PARAMETER {
DCa = 0.6 (um2/ms)
: Ca buffer reaction rates :
k1buf = 30 (/mM ms) : these rates from Sala and Hernandez-Cruz 1990
k2buf = 0.03 (/ms) : and are labeled f and b in
: Quadroni and Knopfel 1994 p. 1916
B = 0.025 (mM) : this is [B] in Quadroni and Knopfel 94 Table 4
: compare above with these rates from
: k1buf = 100 (/mM ms) : Yamada et al. 1989
: k2buf = 0.1 (/ms)
: B = 0.003 (mM)
K2f_ex = 6.3680304e-08 (mA/cm2 mM4) : 3.3e-13 (/umol ms mM4 cm2)*2*FARADAY : Q and K 94
: K2f_ex = 5e-6 (mA/cm2mM2): a value from Lytton and Sejnowski's (LS '91) 5e-6
: (Soma value only - dendrites are different)
cao = 2 (mM) : [Ca]_outside is set constant to 2 mM because it
: is to a good approximation (assumed not to change much in real world).
E_1 = 0.01315 (/mV) : Quadroni and Knopfel 94
E_2 = 0.0255 (/mV) : "
nai = 7.6 (mM) : " : (LS's '91 = 10 mM)
nao = 152 (mM) : " : (LS's '91 = 140 mM)
K2f_ATPase =0.00051137214 (mA/cm2) : 2.65e-9 (/umol ms cm2)*2*FARADAY : type A soma only
: dendrites and type B cell different
f_ATPase = 100 (/mM ms) : simply called f for forward rate in Quadroni Knopfel
b_ATPase = 0.005 (/ms) : 1994 - this one is just called b for backward
factor = 1 (1) : diagnostic for cai concentration in rate eq
mM2M = 1e-3 (1) : mM to M conversion for cai concentration in rate eq
}
ASSIGNED {
v (mV)
diam (um)
ica (mA/cm2)
I (mA/cm2) : same as ica but used for diagnostic purposes
i_Na_Ca_ex (mA/cm2)
i_ATPase (mA/cm2)
cai (mM)
vrat[Nshells] (um3) : vrat[i] equals the volume of a spherical shell in cubic microns
Kd (/mM)
B0 (mM)
ifake (mA/cm2) : fake current used to make solver move
: calculation of breakpt. to same time as currents.
}
STATE {
: ca[0] is equivalent to cai
: ca[] are very small, so specify absolute tolerance
ca[Nshells] (mM) <1e-6>
CaBuffer[Nshells] (mM) <1e-6>
Buffer[Nshells] (mM) <1e-6>
n (1)
}
BREAKPOINT {
SOLVE states METHOD cnexp
SOLVE state METHOD sparse
i_Na_Ca_ex = -K2f_ex * (nai^3 * cao * exp(E_1 * v) - nao^3 * cai * exp(-E_2*v))
i_ATPase = K2f_ATPase * n
I= ica : diagnostic purposes only
ifake=0 : causes solver to execute the breakpoint block at the
: same time as the calculation of the other currents
}
DERIVATIVE states {
: compute state variable n at present v and t
n' = f_ATPase * cai * (1 - n) - b_ATPase * n
}
INITIAL {
factors() : vrat = 0 unless vrat is GLOBAL
n = f_ATPase * cai / (f_ATPase * cai + b_ATPase)
Kd = k1buf/k2buf
B0 = B/(1 + Kd*cai)
FROM i=0 TO Nshells-1 {
cai = 5e-5 : initialization value of 50 uM in mM
ca[i] = cai
Buffer[i] = B0
CaBuffer[i] = B - B0
}
}
LOCAL frat[Nshells] : scales the rate constants for model geometry
LOCAL radii[Nthick] : these are the constant volume thick shells radii
LOCAL drthick[Nthick] : these are simply the delta between the above
: note that r_0 = r, (1/21)(4PI/3)r^3=(4PI/3)(r_i^3-r_(i+1)^3)
: from which we derive r_(i+1) = ( r_i^3 - (1/21) * r_(i+1)^3 )^(1/3)
LOCAL drthick2[Nthick] : in our weird notation will be just drthick[]/2
LOCAL i_ : an index for drthick[]'s
PROCEDURE factors() {
LOCAL r, drthin, drthin2 : the X2 variables are divided by 2 (unusual notation)
r = diam/2 : starts at edge (half diam)
radii[0] = r
FROM i=1 TO Nthick-1 {
radii[i] = ( radii[i-1]^3 - (1/21)*r^3 )^(1/3)
drthick[i-1] = radii[i-1] - radii[i]
drthick2[i-1]=drthick[i-1]/2
}
: if drthick was constant: drthick=r/Nthick : thick shells divided up evenly
: if drthick was constant: drthick2 = drthick/2
:
: to figure out the below note that 3/2 drthin's fit if Nthin=2, 5/2 drthin's fit if Nthin=3...
drthin = 2 * (drthick[0]) / ( 2*Nthin - 1 ) : the outter thick shell divided up
drthin2 = drthin/2 : full thickness of outermost shell
: half thickness of all other shells
vrat[0] = 0
frat[0] = 2*r : where does this get used?
: first do outer thin shells
FROM i=0 TO Nthin-2 {
: whole outermost shell, otherwise outer half of inner shells
vrat[i] = vrat[i] + (4*PI/3) * (3*r^2*drthin2-3*r*drthin2^2+drthin2^3)
r = r - drthin2
frat[i+1] = 4*PI*r*r/drthin
r = r-drthin2
vrat[i+1] = (4*PI/3) * (3*r^2*drthin2 + 3*r*drthin2^2 + drthin2^3)
}
: next do inner thick shells
FROM i=Nthin-1 TO Nshells-2 {
i_ = 1 : special index for drthick starts at second index, one, since
: the zeroth index is where the thin shells are.
if (i==Nthin-1) {
: special case - outer volumne is half a thin shell and inner volumner
: is half a thick shell
vrat[i] = vrat[i] + (4*PI/3) * (3*r^2*drthin2-3*r*drthin2^2+drthin2^3)
r = r - drthin2
frat[i+1] = 4*PI*r*r/(drthin2+drthick2[i_])
r = r - drthick2[i_]
vrat[i+1] = (4*PI/3) * (3*r^2*drthick2[i_] + 3*r*drthick2[i_]^2 + drthick2[i_]^3)
} else {
vrat[i] = vrat[i] + (4*PI/3) * (3*r^2*drthick2[i_]-3*r*drthick2[i_]^2+drthick2[i_]^3)
r = r - drthick2[i_]
frat[i+1] = 4*PI*r*r/drthick[i_]
r = r-drthick2[i_]
vrat[i+1] = (4*PI/3) * (3*r^2*drthick2[i_] + 3*r*drthick2[i_]^2 + drthick2[i_]^3)
}
i_ = i_ + 1
}
}
: LOCAL dsq, dsqvol : can't define local variable in KINETIC block
: or use in COMPARTMENT statement
KINETIC state {
COMPARTMENT i, vrat[i] {ca CaBuffer Buffer}
: note that LONGITUDINAL_DIFFUSION doesn't make sense for spherical shells
~ ca[0] << ((-ica - i_Na_Ca_ex - i_ATPase)*PI*diam*diam /(2*FARADAY))
: ica is Ca efflux from lva and hva mechanisms
: i_Na_Ca_ex is the current from Na-Ca exhanger
: i_ATPase is the current from Ca-ATPase
FROM i=0 TO Nshells-2 {
~ ca[i] <-> ca[i+1] (DCa*frat[i+1], DCa*frat[i+1])
}
: dsq = diam*diam
FROM i=0 TO Nshells-1 {
: dsqvol = dsq*vrat[i]
~ ca[i] + Buffer[i] <-> CaBuffer[i] (k1buf*vrat[i], k2buf*vrat[i])
}
cai = ca[0]
}