NMDA receptor saturation (Chen et al 2001)

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Accession:7988
Experiments and modeling reported in the paper Chen N, Ren J, Raymond LA, and Murphy T (2001) support the hypothesis that glutamate has a relatively lower potency at NMDARs than previously thought from agonist application under equilibrium conditions. Further information and reprint requests are available from Dr T.H. Murphy thmurphy at interchange.ubc.ca
Reference:
1 . Chen N, Ren J, Raymond LA, Murphy TH (2001) Changes in agonist concentration dependence that are a function of duration of exposure suggest N-methyl-D-aspartate receptor nonsaturation during synaptic stimulation. Mol Pharmacol 59:212-9 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Synapse;
Brain Region(s)/Organism:
Cell Type(s):
Channel(s):
Gap Junctions:
Receptor(s): NMDA;
Gene(s): NR2A GRIN2A; NR2B GRIN2B;
Transmitter(s): Glutamate;
Simulation Environment: NEURON;
Model Concept(s): Ion Channel Kinetics;
Implementer(s): Murphy, Tim H [THMurphy at interchange.ubc.ca];
Search NeuronDB for information about:  NMDA; Glutamate;
INDEPENDENT {t FROM 0 TO 1 WITH 1 (ms)}

NEURON {
	POINT_PROCESS NMDA5
	POINTER C
	RANGE C0, C1, C2, D, O, B
	RANGE g, gmax, rb
	GLOBAL Erev, mg, Rb, Ru, Rd, Rr, Ro, Rc
	GLOBAL vmin, vmax
        NONSPECIFIC_CURRENT inmda
}

UNITS {
	(nA) = (nanoamp)
	(mV) = (millivolt)
	(pS) = (picosiemens)
	(umho) = (micromho)
	(mM) = (milli/liter)
	(uM) = (micro/liter)
}

PARAMETER {

	Erev	= 0    (mV)	: reversal potential
	gmax	= 500  (pS)	: maximal conductance
	mg	= 0    (mM)	: external magnesium concentration
	vmin = -120	(mV)
	vmax = 100	(mV)
	
: Rates

	: Destexhe, Mainen & Sejnowski, 1996
	Rb	= 5e-3    (/uM /ms)	: binding 		
	Ru	= 12.9e-3  (/ms)	: unbinding		
	Rd	= 8.4e-3   (/ms)	: desensitization
	Rr	= 6.8e-3   (/ms)	: resensitization 
	Ro	= 46.5e-3   (/ms)	: opening
	Rc	= 73.8e-3   (/ms)	: closing
}

COMMENT
	: Clements et al. 1992
	Rb	= 5e-3    (/uM /ms)	: binding 		
	Ru	= 9.5e-3  (/ms)	: unbinding		
	Rd	= 16e-3   (/ms)	: desensitization
	Rr	= 13e-3   (/ms)	: resensitization 
	Ro	= 25e-3   (/ms)	: opening
	Rc	= 59e-3   (/ms)	: closing

	: Hessler Shirke & Malinow 1993
	Rb	= 5e-3    (/uM /ms)	: binding 		
	Ru	= 9.5e-3  (/ms)	: unbinding		
	Rd	= 16e-3   (/ms)	: desensitization
	Rr	= 13e-3   (/ms)	: resensitization 
	Ro	= 25e-3   (/ms)	: opening
	Rc	= 59e-3   (/ms)	: closing

	: Clements & Westbrook 1991
	Rb	=  5    (uM /s)	: binding 		
	Ru	=  5	(/s)	: unbinding -> gives Kd = Rb/Ru = 1 uM
	Rd	=  4.0  (/s)	: desensitization
	Rr	=  0.3  (/s)	: resensitization 
	Ro	= 10  (/s)	: opening
	Rc	= 322   (/s)	: closing

	: Edmonds & Colquhoun 1992
	Rb	=  5    (uM /s)	: binding 		
	Ru	=  4.7  (/s)	: unbinding		
	Rd	=  8.4  (/s)	: desensitization
	Rr	=  1.8  (/s)	: resensitization 
	Ro	= 46.5  (/s)	: opening
	Rc	= 91.6  (/s)	: closing

	: Lester & Jahr 1992
	Rb	= 5    (uM /s)	: binding 		
	Ru	= 6.7   (/s)	: unbinding		
	Rd	= 15.2  (/s)	: desensitization
	Rr	= 9.4   (/s)	: resensitization 
	Ro	= 83.8  (/s)	: opening
	Rc	= 83.8  (/s)	: closing

ENDCOMMENT


ASSIGNED {
	v		(mV)		: postsynaptic voltage
        inmda               (nA)            : current = g*(v - Erev)
	g 		(pS)		: conductance
	C 		(mM)		: pointer to glutamate concentration

	rb		(/ms)    : binding
}

STATE {
	: Channel states (all fractions)
	C0		: unbound
	C1		: single bound
	C2		: double bound
	D		: desensitized
	O		: open

	B		: fraction free of Mg2+ block
}

INITIAL {
	rates(v)
	C0 = 1
}

BREAKPOINT {
	rates(v)
	SOLVE kstates METHOD sparse

	g = gmax * O * B
      inmda = (1e-6) * g * (v - Erev)

	 
	
}

KINETIC kstates {
	
	rb = Rb * (1e3) * C 

        ~ C0 <-> C1     (2*rb,Ru)
        ~ C1 <-> C2     (rb,2*Ru)
	~ C2 <-> D	(Rd,Rr)
	~ C2 <-> O	(Ro,Rc)

	CONSERVE C0+C1+C2+D+O = 1
}

PROCEDURE rates(v(mV)) {
	TABLE B
	DEPEND mg
	FROM vmin TO vmax WITH 200

	: from Jahr & Stevens

	B = 1 / (1 + exp(0.062 (/mV) * -v) * (mg / 3.57 (mM)))
}



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