Regulation of motoneuron excitability by KCNQ/Kv7 modulators (Lombardo & Harrington 2016)

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Accession:217882
" ... Computer simulations confirmed that pharmacological enhancement of KCNQ/Kv7 channel (M current) activity decreases excitability and also suggested that the effects of inhibition of KCNQ/Kv7 channels on the excitability of spinal MNs do not depend on a direct effect in these neurons but likely on spinal cord synaptic partners. These results indicate that KCNQ/Kv7 channels have a fundamental role in the modulation of the excitability of spinal MNs acting both in these neurons and in their local presynaptic partners. ..."
Reference:
1 . Lombardo J, Harrington MA (2016) Non-reciprocal mechanisms of up- and down-regulation of spinal motoneuron excitability by modulators of KCNQ/Kv7 channels. J Neurophysiol :jn.00446.2016 [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: Spinal motoneuron;
Cell Type(s): Spinal cord L motor neuron alpha;
Channel(s): I Potassium; I K; I Na,t; I M;
Gap Junctions:
Receptor(s):
Gene(s):
Transmitter(s):
Simulation Environment: NEURON;
Model Concept(s): Axonal Action Potentials;
Implementer(s): Lombardo, Joseph [josslomb at gmail.com];
Search NeuronDB for information about:  Spinal cord L motor neuron alpha; I Na,t; I K; I M; I Potassium;
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LombardoHarrington2016
readme.html
Gfluctdv.mod *
ghchan.mod *
kca2.mod *
kdrRL.mod *
Km.mod *
kv1_gp.mod
L_Ca.mod *
mAHP.mod *
na3n.mod
na3rp.mod *
naps.mod *
napsi.mod *
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FR3cablepas.hoc
FRMot3dendNaHH.hoc
gKm0.png
GraphicsKmModulators.hoc
ModifiedFRMotoneuron.hoc
mosinit.hoc
retigabine.png
standard_0.hoc
Tools.ses
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TITLE na3rp
: Na current 
: modified from Jeff Magee. M.Migliore may97
: added sh to account for higher threshold M.Migliore, Apr.2002
: modified by RP to have slow inactivation given in Fleiderivsh et al.

NEURON {
	SUFFIX na3rp
	USEION na READ ena WRITE ina
	RANGE  gbar, ar, sh,ina
	RANGE minf, hinf, mtau, htau, sinf, taus
	GLOBAL qinf, thinf
}

PARAMETER {
	sh   = 8	(mV)
	gbar = 0.010   	(mho/cm2)	
								
	tha  =  -30	(mV)		: v 1/2 for act	
	qa   = 7.2	(mV)		: act slope (4.5)		
	Ra   = 0.4	(/ms)		: open (v)		
	Rb   = 0.124 	(/ms)		: close (v)		

	thi1  = -45	(mV)		: v 1/2 for inact 	
	thi2  = -45 	(mV)		: v 1/2 for inact 	
	qd   = 1.5	(mV)	        : inact tau slope
	qg   = 1.5      (mV)
	mmin=0.02	
	hmin=0.5			
	q10=2
	Rg   = 0.01 	(/ms)		: inact recov (v) 	
	Rd   = .03 	(/ms)		: inact (v)	
	qq   = 10        (mV)
	tq   = -55      (mV)

	thinf  = -50 	(mV)		: inact inf slope	
	qinf  = 4 	(mV)		: inact inf slope 

        a0s=0.001	(/ms)	
        b0s=0.0034	(/ms)
        asvh=-85	(mV) 
        bsvh=-17	(mV) 
        avs=30		(mV)
        bvs=10		(mV)
        ar=1		(1)		: 1=no inact., 0=max inact.
	ena		(mV)            : must be explicitly def. in hoc
	celsius
	v 		(mV)
}


UNITS {
	(mA) = (milliamp)
	(mV) = (millivolt)
	(pS) = (picosiemens)
	(um) = (micron)
} 

ASSIGNED {
	ina 		(mA/cm2)
	thegna		(mho/cm2)
	minf 		hinf 		
	mtau (ms)	htau (ms) 	
	sinf (ms)	taus (ms)
}
 

STATE { m h s}

BREAKPOINT {
        SOLVE states METHOD cnexp
        thegna = gbar*m*m*m*h*s
	ina = thegna * (v - ena)
} 

INITIAL {
	trates(v,ar,sh)
	m=minf  
	h=hinf
	s=sinf
}


       
FUNCTION alps(v(mV)) {  
   alps = a0s*exp((asvh-v)/avs)
}

FUNCTION bets(v(mV)) {
  bets = b0s/(exp((bsvh-v)/bvs)+1)
}

LOCAL mexp, hexp, sexp

DERIVATIVE states {   
        trates(v,ar,sh)      
        m' = (minf-m)/mtau
        h' = (hinf-h)/htau
        s' = (sinf - s)/taus
}

PROCEDURE trates(vm,a2,sh2) {  
        LOCAL  a, b, c, qt
        qt=q10^((celsius-24)/10)
	a = trap0(vm,tha+sh2,Ra,qa)
	b = trap0(-vm,-tha-sh2,Rb,qa)
	mtau = 1/(a+b)/qt
        if (mtau<mmin) {mtau=mmin}
	minf = a/(a+b)

	a = trap0(vm,thi1+sh2,Rd,qd)
	b = trap0(-vm,-thi2-sh2,Rg,qg)
	htau =  1/(a+b)/qt
        if (htau<hmin) {htau=hmin}
	hinf = 1/(1+exp((vm-thinf-sh2)/qinf))
        taus = 1/(alps(vm)+bets(vm))
	c=alps(vm)*taus
        sinf = c+a2*(1-c)
}

FUNCTION trap0(v,th,a,q) {
	if (fabs(v-th) > 1e-6) {
	        trap0 = a * (v - th) / (1 - exp(-(v - th)/q))
	} else {
	        trap0 = a * q
 	}
}	

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