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 late2.mod   ttx-sensitive late sodium channel
 
UNITS {
        (mA) = (milliamp)
        (mV) = (millivolt)
	(S) = (siemens)
}
 
NEURON {
        SUFFIX ls :'l' for late, 's' for sodium    
        USEION na READ ena WRITE ina
        RANGE gnabar, gna, ina
        GLOBAL minf, hinf, htau
}
 
PARAMETER {
        gnabar = 0 (S/cm2)	<0,1e9>              
}
 
STATE {
        m h
}
 
ASSIGNED {
        v (mV)
        celsius (degC)
        ena (mV)
        
	gna (S/cm2)	
	ina (mA/cm2)
        minf hinf 
	htau (ms)
}
 
LOCAL mexp, hexp
 
? currents
BREAKPOINT {
        SOLVE states METHOD cnexp
        m = minf
        gna = gnabar*m*h
	ina = gna*(v - ena)	
}
 
 
INITIAL {
	rates(v)
	m = minf
	h = hinf	
}

? states
DERIVATIVE states {  
        rates(v)
        h' = (hinf-h)/htau       
}

LOCAL q10

? rates
PROCEDURE rates(v(mV)) {  
        TABLE minf, hinf, htau DEPEND celsius FROM -100 TO 100 WITH 200
UNITSOFF
	        :"m" sodium activation system taken from HH
	minf = 1/(1+exp((-51.8-v)/4.6)) :Baker 2000
                :"h" sodium inactivation system
	htau = 1/(0.04 * exp(v/25.5)) + 63.2            :fig 3C
	hinf = 0.9827/(1 + exp(-((v + 55.67)/-6.552)))  :fig 3E 
}
UNITSON

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