TITLE (very)Empirical model for the effect of NK1 receptor activation
COMMENT
The effects of the activation of NK1 receptors are not totally
clear but they seem to include both a membrane conductance change
and an increase in intracellular calcium concentration (assumed
to result from the release of calcium from intracellular buffers)
The dynamics of this receptor should be used in association with
dynamics for intracellular calcium dynamics. It affects all
calciumdependent currents!
We have based this model in the paper by Ito et al, 2002, with the
title: "Substance P mobilizes intracellular calcium and activates
a nonselective cation conductance in rat spiral ganglion neurons."
The model includes therefore two mechanisms:
a) a slow conductance change generating a depolarizing nonspecific
cationic current iNK1R
b) an increase in cai
Details are given in the code, in the form of comments.
The activation of NK1R is subject to shortterm dynamics acting on
SP release & activation:
"Release of substance P is induced by stressful stimuli, and
the magnitude of its release is proportional to the intensity
and frequency of stimulation. More potent and more frequent
stimuli allow diffusion of substance P farther from the site
of release, allowing activation of an approximately 3 to 5times
greater number of NK1 receptorexpressing neurons" (Mantyh, 2002)
We used the shortterm plasticity equations from Fuhrmann et al,
2002, to model the frequency dependent nature of the NK1R activation.
Note however that these equations are being used in a more broad
manner (i.e. the dynamics are intended to encapsulate not only
synaptic release but other mechanisms, such as SP diffusion, which
can give rise to facilitation).
Written by Paulo Aguiar, May 2009
pauloaguiar@fc.up.pt
My thanks to Ted Carnevale for his fantastic help at
The NEURON Forum
"
ENDCOMMENT
NEURON {
POINT_PROCESS NK1_DynSyn
USEION ca WRITE ica
RANGE tau_rise, tau_decay
RANGE U1, tau_rec, tau_fac, stp
RANGE i, g, e, iNK1R, ica, ca_ratio
NONSPECIFIC_CURRENT iNK1R
}
UNITS {
(nA) = (nanoamp)
(mV) = (millivolt)
(molar) = (1/liter)
(mM) = (millimolar)
}
PARAMETER {
tau_rise = 10.0 (ms) : dualexponential conductance profile
tau_decay = 5000.0 (ms) : IMPORTANT: tau_rise < tau_decay
U1 = 1.0 (1) : The parameter U1, tau_rec and tau_fac define _
tau_rec = 0.1 (ms) : the presynaptic SP shortterm plasticity _
tau_fac = 0.1 (ms) : mechanism (see Fuhrmann et al, 2002)
e = 0.0 (mV) : reversal potential
ca_ratio = 0.1 (1) : the increase in cai is assumed here to be proportional to iNK1; this is the constant of proportionality
stp = 1.0 (1) : boolean for synaptic plasticity
}
ASSIGNED {
v (mV)
i (nA)
g (umho)
factor (1)
ica (nA)
iNK1R (nA)
}
STATE {
A
B
}
INITIAL{
LOCAL tp
A = 0
B = 0
tp = (tau_rise*tau_decay)/(tau_decaytau_rise)*log(tau_decay/tau_rise)
factor = exp(tp/tau_rise)+exp(tp/tau_decay)
factor = 1/factor
}
BREAKPOINT {
SOLVE state METHOD cnexp
g = BA
i = g*(ve)
ica = ca_ratio * i
: the ica current is "silenced" by removing ica from the total current
iNK1R = i  ica
: this way we have an increase in cai without a contribution of ica in membrane currents
}
DERIVATIVE state{
A' = A/tau_rise
B' = B/tau_decay
}
NET_RECEIVE (weight, Pv, P, Use, t0 (ms)){
INITIAL{
P=1
Use=0
t0=t
}
if(stp){
Use = Use * exp((tt0)/tau_fac)
Use = Use + U1*(1Use)
P = 1(1 P) * exp((tt0)/tau_rec)
Pv = Use * P
P = P  Use * P
t0 = t
A = A + weight*factor*Pv
B = B + weight*factor*Pv
} else {
A = A + weight*factor
B = B + weight*factor
}
}
