: Model and most parameters from Wang, Chen, Nolan and Siegelbaum, Neuron, 2002
: Some parameters tuned to match findings of Gambardella, Pignatelli and Belluzi 2012
: The h-current in the Substantia Nigra pars Compacta Neurons : A Re-examination
: PLoS ONE December 2012 7:12 e52329
: Adapted by Tim Rumbell, 2017, thrumbel@us.ibm.com
NEURON {
SUFFIX hcn
NONSPECIFIC_CURRENT i
RANGE i, ehcn, g, gbar
EXTERNAL apc_metap, fpc_metap
GLOBAL a0, b0, ah, bh, ac, bc, aa0, ba0
GLOBAL aa0, ba0, aah, bah, aac, bac
GLOBAL kon, koff, b, bf, gca, shift
GLOBAL Vhalf, vh1, vh2, vh_shift, avh1, avh2, avh_shift
RANGE ai
}
UNITS {
(mV) = (millivolt)
(molar) = (1/liter)
(mM) = (millimolar)
(mA) = (milliamp)
(S) = (siemens)
}
PARAMETER {
gbar = 0.0 (S/cm2)
ehcn = -44 (mV) : parameter from Gambardella 2012
: : Params established using least squares non linear fitting from orig params +- 25%
: a0 = .0023 (/ms) : parameters for alpha and beta
: b0 = .0022 (/ms)
: ah = -93.9898 (mV)
: bh = -62.7310 (mV)
: ac = -0.1137 (/mV)
: bc = 0.1203 (/mV)
: aa0 = 0.1203 (/ms) : parameters for alphaa and betaa
: ba0 = 0.0042 (/ms)
: aah = -109.7611 (mV)
: bah = -27.6119 (mV)
: aac = -0.0678 (/mV)
: bac = 0.07 (/mV)
: kon = 1.327 (/mM-ms) : cyclic AMP binding parameters
: koff = 1.217e-05 (/ms)
: b = 101.1513
: bf = 17.5464
: Params established from using least squares non linear fitting
: Used original params +- 100%
: Used 26 different values for Vhalf
: Boltzmann slope 7.5
: cAMP effect on half act: +3 mV @ 1e-5 mM; +10 mV @ 0.01 mM
: tau tuned to Amendola 2012 fig 7b, Vhalf = half act +4.9 mV (from Amendola)
: cAMP binding rates left as in Siegelbaum
:::These are set to tuned values
a0 = .00032743 (/ms) : parameters for alpha and beta
b0 = .00029334 (/ms)
ac = -0.1103 (/mV)
bc = 0.1025 (/mV)
aa0 = 0.0011 (/ms) : parameters for alphaa and betaa
ba0 = 0.0164 (/ms)
aac = -0.0774 (/mV)
bac = 0.1486 (/mV)
::: These are set according to the Vhalf kinetic parameter:
Vhalf = -90.0 (mV)
vh1 = 1.057
vh2 = 79.3
avh1 = 1.886
avh2 = 164.1
::: And the rest are left at default
kon = 3.086 (/mM-ms) : cyclic AMP binding parameters
koff = 4.4857e-05 (/ms)
b = 80
bf = 8.94
ai = 1e-05 (mM) : concentration cyclic AMP
gca = 1 : relative conductance of the bound state
shift = 0 (mV) : shift in voltage dependence
q10v = 4 : q10 value from Magee 1998
q10a = 1.5 : estimated q10 for the cAMP binding reaction
celsius (degC)
}
ASSIGNED {
v (mV)
g (S/cm2)
i (mA/cm2)
alpha (/ms)
beta (/ms)
alphaa (/ms)
betaa (/ms)
vh_shift
avh_shift
ah (mV)
bh (mV)
aah (mV)
bah (mV)
}
STATE {
c
cac
o
cao
}
INITIAL {
setVhalf(Vhalf)
SOLVE kin STEADYSTATE sparse
}
BREAKPOINT {
SOLVE kin METHOD sparse
g = gbar*(o + cao*gca)
i = g*(v-ehcn)
}
KINETIC kin {
LOCAL qa
qa = q10a^((celsius-22 (degC))/10 (degC)) : original
: qa = q10a^((celsius-35 (degC))/10 (degC))
rates(v)
~ c <-> o (alpha, beta)
~ c <-> cac (kon*qa*ai/bf,koff*qa*b/bf)
~ o <-> cao (kon*qa*ai, koff*qa)
~ cac <-> cao (alphaa, betaa)
CONSERVE c + cac + o + cao = 1
}
PROCEDURE rates(v(mV)) {
LOCAL qv
qv = q10v^((celsius-22 (degC))/10 (degC)) : original
: qv = q10v^((celsius-37 (degC))/10 (degC))
if (v > -200) {
alpha = a0*qv / (1 + exp(-(v-ah-shift)*ac))
beta = b0*qv / (1 + exp(-(v-bh-shift)*bc))
alphaa = aa0*qv / (1 + exp(-(v-aah-shift)*aac))
betaa = ba0*qv / (1 + exp(-(v-bah-shift)*bac))
} else {
alpha = a0*qv / (1 + exp(-((-200)-ah-shift)*ac))
beta = b0*qv / (1 + exp(-((-200)-bh-shift)*bc))
alphaa = aa0*qv / (1 + exp(-((-200)-aah-shift)*aac))
betaa = ba0*qv / (1 + exp(-((-200)-bah-shift)*bac))
}
}
PROCEDURE setVhalf(Vhalf(mV)) {
vh_shift = Vhalf*vh1+vh2
:avh_shift = vh_shift+avh1
avh_shift = Vhalf*avh1+avh2
ah = -87.7 + vh_shift
bh = -51.7 + vh_shift
aah = -94.2 + avh_shift
bah = -35.5 + avh_shift
}