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) Nonreciprocal mechanisms in up- and downregulation of spinal motoneuron excitability by modulators of KCNQ/Kv7 channels. J Neurophysiol 116:2114-2124 [PubMed]
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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 lumbar motor neuron alpha ACh cell;
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 lumbar motor neuron alpha ACh cell; 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
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mAHP.mod *
na3n.mod
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FRMot3dendNaHH.hoc
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GraphicsKmModulators.hoc
ModifiedFRMotoneuron.hoc
mosinit.hoc
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TITLE Motoneuron L-type Calcium channels
:
: The parameters for this current come from V. Booth et al. J Neurophysiol 78:3371-3385, 1997
: Iterative equations
: Modified by RP to provide calcium to a separate pool (caL)and to have adjustable equilibrium
: potential vca


NEURON {
	SUFFIX L_Ca
	USEION caL READ ecaL WRITE icaL VALENCE 2
	RANGE gcabar,icaL,m_inf,m
	GLOBAL vca,theta_m,kappa_m
}


UNITS {
	(mA) = (milliamp)
	(mV) = (millivolt)
}

PARAMETER {
	gcabar  = 0.0003  (mho/cm2)
	ecaL		(mV)	: eca can't be set here, only in hoc
:	celcius = 36	(degC)
	dt		(ms)
	tau_m	= 20	(ms)
	v		(mV)
        vca=80		(mV)
	theta_m = -30   (mV)
	kappa_m = -6	(-mV)
}

STATE {
	m
}

ASSIGNED {
	icaL		(mA/cm2)
	m_inf
	tadj
}

BREAKPOINT {
	SOLVE states METHOD cnexp
	icaL = gcabar * m * (v - vca)  :I have tried this as m*m also
}

DERIVATIVE states {
	evaluate_fct(v)
	m' = (m_inf - m) / tau_m
}

UNITSOFF
INITIAL {

:
:  Q10 was assumed to be 3 for both currents
:
:	tadj = 3.0 ^ ((celsius-36)/ 10 )

	evaluate_fct(v)
	m = m_inf
}

PROCEDURE evaluate_fct(v(mV)) {

	m_inf = 1 / (1 + (Exp((v - theta_m)/ kappa_m))): / tadj

}

FUNCTION vtrap(x,y) {
	if (fabs(x/y) < 1e-6) {
		vtrap = y*(1 - x/y/2)
	}else{
		vtrap = x/(Exp(x/y)-1)
	}
}

FUNCTION Exp(x) {
	if (x < -100) {
		Exp = 0
	}else{
		Exp = exp(x)
	}
}