Neurophysiological impact of inactivation pathways in A-type K+ channels (Fineberg et al 2012)

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Accession:145672
These models predict the differential effects of varying pathways of inactivation (closed state inactivation, CSI, or open state inactivation, OSI). Specifically, Markov models of Kv4 potassium channels with CSI or CSI+OSI were inserted into the CA1 pyramidal neuron model from Migliore et al (1999; ModelDB accession #2796) to determine the neurophysiological impact of inactivation pathways. Furthermore, Markov models of Kv4.2 and Kv3.4 channels are used to illustrate a method by which to test what pathway of inactivation a channel uses.
Reference:
1 . Fineberg JD, Ritter DM, Covarrubias M (2012) Modeling-independent elucidation of inactivation pathways in recombinant and native A-type Kv channels. J Gen Physiol 140:513-27 [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; Channel/Receptor;
Brain Region(s)/Organism:
Cell Type(s): Hippocampus CA1 pyramidal GLU cell;
Channel(s): I Na,t; I A; I K;
Gap Junctions:
Receptor(s):
Gene(s): Kv4.2 KCND2; Kv3.4 KCNC4;
Transmitter(s):
Simulation Environment: NEURON; IonChannelLab;
Model Concept(s): Ion Channel Kinetics; Markov-type model;
Implementer(s): Ritter, David [david.ritter at jefferson.edu];
Search NeuronDB for information about:  Hippocampus CA1 pyramidal GLU cell; I Na,t; I A; I K;
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Fineberg_et_al_2012
IonChannelLab Files
README.html
Kv4_csi.mod
Kv4_csiosi.mod
migliore_kaprox.mod *
migliore_kdrca1.mod *
migliore_na3.mod *
migliore_nax.mod *
csi.hoc
csin160_mod.nrn
csiosi.hoc
csiosin160_mod.nrn
Figure11C CSI.hoc
Figure11C CSIOSI.hoc
Figure11D.hoc
Figure11E.hoc
graphavailability.ses
graphvoltage.ses
iclamp250.ses
iclamp40.ses
mosinit.hoc
n160_mod.nrn *
screenshot1.png
screenshot2.png
                            
:Kv4 CSI+OSI Markov model from Fineberg, Ritter and Covarrubias J Gen Physiol (2012)
:for scheme see Fig. S1 and Table S1 or file "IonChannelLab Files/Kv4 CSIOSI.ichl"
:based on Amarillo et al. J Physiol (2008), Dougherty et al J Gen Physiol (2008), 
:and Migliore et al J Comp Neurosci(1999)
:last edited 10-06-2012 by DMR

NEURON {
	SUFFIX kv4csiosi
	USEION k READ ek WRITE ik
        RANGE g, gmax				
}

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

PARAMETER {
      	gmax = 0.00	(mho/cm2)		
      	celsius 	(deg C)			
      	F = 9.6485e4 				:Faraday constant
      	R = 8.3145e3 				:Gas constant
	a = 7			(/ms)		:alpha transitions
	za = 0.315646648				
      	b = .090		(/ms)		:beta transitions
      	zb = -2.062276				
	c = 1.01216107		(/ms)		:gamma transitions
	zc = 0.500095665
	d = 2.498881		(/ms)		:delta transitions
	zd = -1.1546687
	k = 7.69049072		(/ms)		:epsilon transition
	zk = 0.05502051
	l = 4.38562354		(/ms)		:phi transition
	zl = -0.07092366 
	f = 0.277130485				:closed-state inactivation allosteric factor f
	q = 1.01314807				:closed-state inactivation allosteric factor g
	kci = 0.121900093	(/ms)		:closed to inactivated transitions
	kic = 0.0017935468 	(/ms)		:inactivated to closed transitions
	koi = 0.5195		(/ms)		:kappa1 transition
	kio = 0.0436		(/ms)		:lambda1 transition
	kii2 = 0.1475		(/ms)		:kappa2 transition
	ki2i = 0.0333		(/ms)		:lambda2 transition
}

ASSIGNED {
     	v    (mV)
     	ek   (mV)
     	g    (S/cm2)
      	ik   (mA/cm2)
      	kC01f  (/ms)
      	kC01b  (/ms)
	kC12f  (/ms)
     	kC12b  (/ms)
	kC23f  (/ms)
     	kC23b  (/ms)
	kC34f  (/ms)
     	kC34b  (/ms)
	kC45f  (/ms)
 	kC45b  (/ms)
	kCOf  (/ms)
      	kCOb  (/ms)
      	kCI0f  (/ms)
      	kCI0b  (/ms)
	kCI1f  (/ms)
     	kCI1b  (/ms)
	kCI2f  (/ms)
     	kCI2b  (/ms)
	kCI3f  (/ms)
     	kCI3b  (/ms)
	kCI4f  (/ms)
 	kCI4b  (/ms)
	kCI5f  (/ms)
      	kCI5b  (/ms)
      	kI01f  (/ms)
      	kI01b  (/ms)
	kI12f  (/ms)
     	kI12b  (/ms)
	kI23f  (/ms)
     	kI23b  (/ms)
	kI34f  (/ms)
     	kI34b  (/ms)
	kI45f  (/ms)
 	kI45b  (/ms)
	kOIf   (/ms)
	kOIb   (/ms)
	kII2f  (/ms)
	kII2b  (/ms)
}

STATE { C0 C1 C2 C3 C4 C5 I0 I1 I2 I3 I4 I5 O I6 I7 }
BREAKPOINT {
      SOLVE states METHOD sparse
      g = gmax * O
      ik = g * (v - ek)
}

INITIAL { SOLVE states STEADYSTATE sparse}

KINETIC states {   		
        rates(v)
	~C0 <-> C1 (kC01f,kC01b)
	~C1 <-> C2 (kC12f,kC12b)
	~C2 <-> C3 (kC23f,kC23b)
	~C3 <-> C4 (kC34f,kC34b)
	~C4 <-> C5 (kC45f,kC45b)
	~C5 <-> O (kCOf,kCOb)
	~C0 <-> I0 (kCI0f,kCI0b)
	~C1 <-> I1 (kCI1f,kCI1b)
	~C2 <-> I2 (kCI2f,kCI2b)
	~C3 <-> I3 (kCI3f,kCI3b)
	~C4 <-> I4 (kCI4f,kCI4b)
	~C5 <-> I5 (kCI5f,kCI5b)
	~I0 <-> I1 (kI01f,kI01b)
	~I1 <-> I2 (kI12f,kI12b)
	~I2 <-> I3 (kI23f,kI23b)
	~I3 <-> I4 (kI34f,kI34b)
	~I4 <-> I5 (kI45f,kI45b)
	~O <-> I6 (kOIf, kOIb)
	~I6 <-> I7 (kII2f, kII2b)
	CONSERVE C0+C1+C2+C3+C4+C5+I0+I1+I2+I3+I4+I5+O+I6+I7=1
}

PROCEDURE rates(v(millivolt)) {

      kC01f = 4*a*exp(za*v*F/(R*(273.16+celsius)))		:closed to open pathway transitions
      kC01b = b*exp(zb*v*F/(R*(273.16+celsius)))
      kC12f = 3*a*exp(za*v*F/(R*(273.16+celsius)))
      kC12b = 2*b*exp(zb*v*F/(R*(273.16+celsius)))
      kC23f = 2*a*exp(za*v*F/(R*(273.16+celsius)))
      kC23b = 3*b*exp(zb*v*F/(R*(273.16+celsius)))
      kC34f = a*exp(za*v*F/(R*(273.16+celsius)))
      kC34b = 4*b*exp(zb*v*F/(R*(273.16+celsius)))
      kC45f = c*exp(zc*v*F/(R*(273.16+celsius)))
      kC45b = d*exp(zd*v*F/(R*(273.16+celsius)))
      kCOf = k*exp(zk*v*F/(R*(273.16+celsius)))
      kCOb = l*exp(zl*v*F/(R*(273.16+celsius)))
      kCI0f = kci*(f^4)					:closed to inactivated transitions
      kCI0b = kic/(f^4) 
      kCI1f = kci*(f^3)
      kCI1b = kic/(f^3)
      kCI2f = kci*(f^2)
      kCI2b = kic/(f^2)
      kCI3f = kci*(f)
      kCI3b = kic/(f)
      kCI4f = kci
      kCI4b = kic
      kCI5f = kci*q
      kCI5b = kic/q
      kI01f = 4*(1/f)*a*exp(za*v*F/(R*(273.16+celsius)))	:closed to inactivated transitions
      kI01b = d*b*exp(zb*v*F/(R*(273.16+celsius)))
      kI12f = 3*(1/f)*a*exp(za*v*F/(R*(273.16+celsius)))
      kI12b = 2*f*b*exp(zb*v*F/(R*(273.16+celsius)))
      kI23f = 2*(1/f)*a*exp(za*v*F/(R*(273.16+celsius)))
      kI23b = 3*f*b*exp(zb*v*F/(R*(273.16+celsius)))
      kI34f = (1/f)*a*exp(za*v*F/(R*(273.16+celsius)))
      kI34b = 4*f*b*exp(zb*v*F/(R*(273.16+celsius)))
      kI45f = q*c*exp(zc*v*F/(R*(273.16+celsius)))
      kI45b = (1/q)*d*exp(zd*v*F/(R*(273.16+celsius)))
      kOIf = koi						:open to inactivated transitions		
      kOIb = kio
      kII2f = kii2					
      kII2b = ki2i
}