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 lumbar motor neuron alpha 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 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
L_Ca.mod *
mAHP.mod *
na3n.mod
na3rp.mod *
naps.mod *
napsi.mod *
buttons.png
ctrl.png
FR3cablepas.hoc
FRMot3dendNaHH.hoc
gKm0.png
GraphicsKmModulators.hoc
ModifiedFRMotoneuron.hoc
mosinit.hoc
retigabine.png
standard_0.hoc
Tools.ses
XE991.png
                            
 COMMENT
 
 kca2.mod
 
 Calcium-dependent potassium channel
 Based on
 Pennefather (1990) -- sympathetic ganglion cells
 taken from
 Reuveni et al (1993) -- neocortical cells
 
 Author: Zach Mainen, Salk Institute, 1995, zach@salk.edu
 modified Jan,2000 by RKP;modified July 2005 to include a contribution from calcium
flowing through L channels
 	
 ENDCOMMENT

 NEURON {
 	SUFFIX kca2
 	USEION k READ ek WRITE ik
 	USEION ca READ ica WRITE cai
  USEION caL READ icaL 	
  RANGE n, g,ik,cai,ica,icaL,depth1,taur1,depth2,taur2
 	GLOBAL Ra, Rb, caix
 }
 
 UNITS {
 	(mA) = (milliamp)
 	(mV) = (millivolt)
 	(S) = (siemens)
 	(um) = (micron)
 	(molar) = (1/liter)			: moles do not appear in units
 	(mM)	= (millimolar)
 	(msM)	= (ms mM)
 	FARADAY = (faraday) (coulomb)
 } 
 
 PARAMETER {
 	g = 0.03   	(S/cm2)	
 	v 		(mV)
 	cai  		(mM)
 	caix = 2	
  cainf=0.0001
 	depth1	= .1	(um)		: depth of shell
 	taur1	= 20	(ms)		: rate of calcium removal
 	depth2	= 10	(um)		: depth of shell
 	taur2	= 200	(ms)		: rate of calcium removal
								
  Ra   = 0.1		: max act rate  
 	Rb   = 0.1		: max deact rate 
 
 	celsius		(degC)
 } 
 
 
 ASSIGNED {
 	ik 		(mA/cm2)
	 ica (mA/cm2)
 	icaL (mA/cm2)
 	ek		(mV)
 	ninf
 	ntau 		(ms)	
  drive_channel1	(mM/ms)
  drive_channel2	(mM/ms)
 }
  
 
 STATE { 
 n 
 ca (mM)
	caL (mM)
}
 
 INITIAL { 
	ca=cainf
 caL=0
 cai=cainf
 rates(cai)
 	n = ninf
 }
 
 BREAKPOINT {
         SOLVE states METHOD cnexp
 	ik =  g *n* (v - ek)
 } 
 

DERIVATIVE states {  
 	drive_channel1 =  - (10000) * ica/ (2 * FARADAY * depth1)
 	if (drive_channel1 <= 0.) { drive_channel1 = 0. }	: cannot pump inward
 	ca' = drive_channel1 + (cainf-ca)/taur1
 	drive_channel2 =  - (10000) * icaL/ (2 * FARADAY * depth2)
 	if (drive_channel2 <= 0.) { drive_channel2 = 0. }	: cannot pump inward
 	caL' = drive_channel2 + (cainf-caL)/taur2
 	cai = ca + caL

          rates(cai)    
         n' = (ninf-n)/ntau
}
PROCEDURE rates(cai(mM)) {  LOCAL a,b
							UNITSOFF
         a = Ra * (1e3*(cai  -cainf))^caix		: rate constant depends on cai in uM
         b = Rb
         ntau = 1/(a+b)
        	ninf = a*ntau
					UNITSON
 }

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