Dorsal root ganglion (DRG) neuronal model (Kovalsky et al. 2009)

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Accession:140038
This model, diverged from oscillatory parameters seen in live cells and failed to produce characteristic ectopic discharge patterns. Here we show that use of a more complete set of Na+ conductances--which includes several delayed components--enables simulation of the entire repertoire of oscillation-triggered electrogenic phenomena seen in live dorsal root ganglion (DRG) neurons. This includes a physiological window of induction and natural patterns of spike discharge. An INa+ component at 2-20 ms was particularly important, even though it represented only a tiny fraction of overall INa+ amplitude. With the addition of a delayed rectifier IK+ the singlet firing seen in some DRG neurons can also be simulated. The model reveals the key conductances that underlie afferent ectopia, conductances that are potentially attractive targets in the search for more effective treatments of neuropathic pain.
Reference:
1 . Kovalsky Y, Amir R, Devor M (2009) Simulation in sensory neurons reveals a key role for delayed Na+ current in subthreshold oscillations and ectopic discharge: implications for neuropathic pain. J Neurophysiol 102:1430-42 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Neuron or other electrically excitable cell;
Brain Region(s)/Organism:
Cell Type(s): Dorsal Root Ganglion (DRG) cell;
Channel(s): I K; I Sodium; Late Na;
Gap Junctions:
Receptor(s):
Gene(s):
Transmitter(s):
Simulation Environment: NEURON;
Model Concept(s): Bursting; Ion Channel Kinetics; Pathophysiology;
Implementer(s): Devor, Marshall [marshlu at vms.huji.ac.il];
Search NeuronDB for information about:  I K; I Sodium; Late Na;
TITLE shift_hh_6.mod  
 
COMMENT
shift HH in 6 mV to the right. 
v1/2 of minf is -34.12 and the slope factor is 9.146. 
v1/2 of hinf is -56.39 and the slope factor is 7.22.
ENDCOMMENT
 
UNITS {
        (mA) = (milliamp)
        (mV) = (millivolt)
	(S) = (siemens)
}
 
? interface
NEURON {
        SUFFIX Shh_6
        USEION na READ ena WRITE ina
        USEION k READ ek WRITE ik
        NONSPECIFIC_CURRENT il
        RANGE gnabar, gkbar, gl, el, gna, gk, ina
        GLOBAL minf, hinf, ninf, mtau, htau, ntau
}
 
PARAMETER {
        gnabar = 0 (S/cm2)	<0,1e9>
        gkbar = 0 (S/cm2)	<0,1e9>
        gl = 0 (S/cm2)	<0,1e9>
        el = 0 (mV)
}
 
STATE {
        m h n
}
 
ASSIGNED {
        v (mV)
        celsius (degC)
        ena (mV)
        ek (mV)

	gna (S/cm2)
	gk (S/cm2)
        ina (mA/cm2)
        ik (mA/cm2)
        il (mA/cm2)
        minf hinf ninf
	mtau (ms) htau (ms) ntau (ms)
}
 
LOCAL mexp, hexp, nexp        
 
? currents
BREAKPOINT {
        SOLVE states METHOD cnexp
        gna = gnabar*m*m*m*h
	ina = gna*(v - ena)
        gk = gkbar*n*n*n*n
	ik = gk*(v - ek)      
        il = gl*(v - el)
}
 
 
INITIAL {
	rates(v)
	m = minf
	h = hinf
	n = ninf
}

? states
DERIVATIVE states {  
        rates(v)
        m' =  (minf-m)/mtau
        h' = (hinf-h)/htau
        n' = (ninf-n)/ntau
}
 
LOCAL q10


? rates
PROCEDURE rates(v(mV)) {  :Computes rate and other constants at current v.
                      :Call once from HOC to initialize inf at resting v.
        LOCAL  alpha, beta, sum
        TABLE minf, mtau, hinf, htau, ninf, ntau DEPEND celsius FROM -100 TO 100 WITH 200

UNITSOFF
        q10 = 3^((celsius - 6.3)/10)
                :"m" sodium activation system
        alpha = .1 * vtrap(-(v+34),10)
        beta =  4 * exp(-(v+59)/18)
        sum = alpha + beta
	mtau = 1/(q10*sum)
        minf = alpha/sum
                :"h" sodium inactivation system
        alpha = .07 * exp(-(v+59)/20)
        beta = 1 / (exp(-(v+29)/10) + 1)
        sum = alpha + beta
	htau = 1/(q10*sum)
        hinf = alpha/sum
                :"n" potassium activation system
        alpha = .01*vtrap(-(v+55),10) 
        beta = .125*exp(-(v+65)/80)
	sum = alpha + beta
        ntau = 1/(q10*sum)
        ninf = alpha/sum
}
 
FUNCTION vtrap(x,y) {  :Traps for 0 in denominator of rate eqns.
        if (fabs(x/y) < 1e-6) {
                vtrap = y*(1 - x/y/2)
        }else{
                vtrap = x/(exp(x/y) - 1)
        }
}
 
UNITSON

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