TITLE N-type calcium current (Cav2.2)
COMMENT
neuromodulation is added as functions:
modulation = 1 + damod*(maxMod-1)*level
where:
damod [0]: is a switch for turning modulation on or off {1/0}
maxMod [1]: is the maximum modulation for this specific channel (read from the param file)
e.g. 10% increase would correspond to a factor of 1.1 (100% +10%) {0-inf}
level [0]: is an additional parameter for scaling modulation.
Can be used simulate non static modulation by gradually changing the value from 0 to 1 {0-1}
[] == default values
{} == ranges
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UNITS {
(mV) = (millivolt)
(mA) = (milliamp)
(S) = (siemens)
(molar) = (1/liter)
(mM) = (millimolar)
FARADAY = (faraday) (coulomb)
R = (k-mole) (joule/degC)
}
NEURON {
THREADSAFE
SUFFIX can
USEION ca READ cai, cao WRITE ica VALENCE 2
RANGE pbar, ica
RANGE damod, maxMod, level, max2, lev2
}
PARAMETER {
pbar = 0.0 (cm/s)
a = 0.21
:q = 1 : room temperature 22-25 C
q = 2 : body temperature 35 C
damod = 0
maxMod = 1
level = 0
max2 = 1
lev2 = 0
}
ASSIGNED {
v (mV)
ica (mA/cm2)
eca (mV)
celsius (degC)
cai (mM)
cao (mM)
minf
mtau (ms)
hinf
htau (ms)
}
STATE { m h }
BREAKPOINT {
SOLVE states METHOD cnexp
ica = pbar*m*m*(h*a+1-a)*ghk(v, cai, cao) *modulation()
}
INITIAL {
rates()
m = minf
h = hinf
}
DERIVATIVE states {
rates()
m' = (minf-m)/mtau*q
h' = (hinf-h)/htau*q
}
PROCEDURE rates() {
UNITSOFF
minf = 1/(1+exp((v-(-3))/(-8)))
:mtau = (0.06+1/(0.033*exp((v-(-36))/18)+0.35*exp((v-15)/-44)))*2
mtau = (0.06+1/(exp((v-25)/18)+exp((v-(-31))/-44)))*2
hinf = 1/(1+exp((v-(-74.8))/6.5))
htau = 70
UNITSON
}
FUNCTION ghk(v (mV), ci (mM), co (mM)) (.001 coul/cm3) {
LOCAL z, eci, eco
z = (1e-3)*2*FARADAY*v/(R*(celsius+273.15))
if(z == 0) {
z = z+1e-6
}
eco = co*(z)/(exp(z)-1)
eci = ci*(-z)/(exp(-z)-1)
ghk = (1e-3)*2*FARADAY*(eci-eco)
}
FUNCTION modulation() {
: returns modulation factor
modulation = 1 + damod * ( (maxMod-1)*level + (max2-1)*lev2 )
if (modulation < 0) {
modulation = 0
}
}
COMMENT
Model is based on mixed data. Activation curve is from neostriatal
medium spinal neurons of adult P28+ rats [1, Fig.12F], unspecified
recording temperature. Potentials were not corrected for the liquid
junction potential, which was estimated to be 7 mV. Activation time
constant is from the rodent neuron culture (both rat and mouse cells),
room temperature 22-25 C [2, Fig.15B]. Inactivation data is from human
(HEK) cells [3, Tab.1, Tab.2], supposedly at room temperature.
Kinetics of m2h type is used [2, Fig.5]. Activation of m2 type is
fitted to the experimental data [1,4], activation time constant [2]
is scaled up as well. Original NEURON model [5,4] was modified by
Alexander Kozlov . Activation time constant was refitted
to avoid singularity in the expression.
[1] Bargas J, Howe A, Eberwine J, Cao Y, Surmeier DJ (1994) Cellular
and molecular characterization of Ca2+ currents in acutely isolated,
adult rat neostriatal neurons. J Neurosci 14(11 Pt 1):6667-86.
[2] Kasai H, Neher E (1992) Dihydropyridine-sensitive and
omega-conotoxin-sensitive calcium channels in a mammalian
neuroblastoma-glioma cell line. J Physiol 448:161-88.
[3] McNaughton NC, Randall AD (1997) Electrophysiological properties of
the human N-type Ca2+ channel: I. Channel gating in Ca2+, Ba2+ and Sr2+
containing solutions. Neuropharmacology 36(7):895-915.
[4] Evans RC, Maniar YM, Blackwell KT (2013) Dynamic modulation of
spike timing-dependent calcium influx during corticostriatal upstates. J
Neurophysiol 110(7):1631-45.
[5] Wolf JA, Moyer JT, Lazarewicz MT, Contreras D, Benoit-Marand M,
O'Donnell P, Finkel LH (2005) NMDA/AMPA ratio impacts state transitions
and entrainment to oscillations in a computational model of the nucleus
accumbens medium spiny projection neuron. J Neurosci 25(40):9080-95.
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