TITLE HVA L-type calcium current (Cav1.2)
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
ENDCOMMENT
UNITS {
(mV) = (millivolt)
(mA) = (milliamp)
(S) = (siemens)
(molar) = (1/liter)
(mM) = (millimolar)
FARADAY = (faraday) (coulomb)
R = (k-mole) (joule/degC)
}
NEURON {
THREADSAFE
SUFFIX cal12
USEION cal READ cali, calo WRITE ical VALENCE 2
RANGE pbar, ical
RANGE damod, maxMod, level, max2, lev2
}
PARAMETER {
pbar = 0.0 (cm/s)
a = 0.17
: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)
ical (mA/cm2)
ecal (mV)
celsius (degC)
cali (mM)
calo (mM)
minf
mtau (ms)
hinf
htau (ms)
}
STATE { m h }
BREAKPOINT {
SOLVE states METHOD cnexp
ical = pbar*m*(h*a+1-a)*ghk(v, cali, calo) *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-(-8.9))/(-6.7)))
:mtau = 0.06+1/(0.06*exp((v-(-46))/20)+0.41*exp((v-26)/-48))
mtau = 0.06+1/(exp((v-10)/20)+exp((v-(-17))/-48))
hinf = 1/(1+exp((v-(-13.4))/11.9))
htau = 44.3
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
Activation curve was reconstructed for cultured NAc neurons from P5-P32
Charles River rat pups [1]. Activation time constant is from the
rodent neuron culture (both rat and mouse cells), room temperature 22-25
C [2, Fig.15A]. Inactivation curve of CaL v1.3 current was taken from HEK
cells [3, Fig.2 and p.819] at room temperature.
Original NEURON model by Wolf (2005) [4] was modified by Alexander Kozlov
. Kinetics of m1h type was used [5,6]. Activation
time constant was refitted to avoid singularity.
[1] Churchill D, Macvicar BA (1998) Biophysical and pharmacological
characterization of voltage-dependent Ca2+ channels in neurons isolated
from rat nucleus accumbens. J Neurophysiol 79(2):635-47.
[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] Bell DC, Butcher AJ, Berrow NS, Page KM, Brust PF, Nesterova A,
Stauderman KA, Seabrook GR, Nurnberg B, Dolphin AC (2001) Biophysical
properties, pharmacology, and modulation of human, neuronal L-type
(alpha(1D), Ca(V)1.3) voltage-dependent calcium currents. J Neurophysiol
85:816-827.
[4] 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.
[5] Evans RC, Morera-Herreras T, Cui Y, Du K, Sheehan T, Kotaleski JH,
Venance L, Blackwell KT (2012) The effects of NMDA subunit composition on
calcium influx and spike timing-dependent plasticity in striatal medium
spiny neurons. PLoS Comput Biol 8(4):e1002493.
[6] Tuckwell HC (2012) Quantitative aspects of L-type Ca2+ currents. Prog
Neurobiol 96(1):1-31.
ENDCOMMENT