Factors contribution to GDP-induced [Cl-]i transients (Lombardi et al 2019)

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Accession:253369
This models are used to evaluate which factors influence the GDP (giant depolarizing potential) induced [Cl-]I transients based on a initial model of P. Jedlicka
Reference:
1 . Lombardi A, Jedlicka P, Luhmann HJ, Kilb W (2019) Interactions Between Membrane Resistance, GABA-A Receptor Properties, Bicarbonate Dynamics and Cl-Transport Shape Activity-Dependent Changes of Intracellular Cl- Concentration Int J of Mol Sci [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Neuron or other electrically excitable cell; Dendrite; Synapse;
Brain Region(s)/Organism: Mouse; Hippocampus;
Cell Type(s): Hippocampus CA3 pyramidal GLU cell;
Channel(s):
Gap Junctions:
Receptor(s): GabaA;
Gene(s):
Transmitter(s): Gaba;
Simulation Environment: NEURON;
Model Concept(s): Synaptic Plasticity;
Implementer(s):
Search NeuronDB for information about:  Hippocampus CA3 pyramidal GLU cell; GabaA; Gaba;
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LombardiEtAl2019
Isolated_Dendrite_gPas__Fig1
cldif_CA3_NKCC1_HCO3.mod *
gabaA_Cl_HCO3.mod *
VDpas.mod *
vecevent.mod *
cell_isolated_dendrite.hoc
GABA-Stim_long_isolated_dendrite.hoc
GABA-Stim_PSC_isolated_dendrite.hoc
GABA-Stim_PSC_isolated_dendrite_Div_gPas.hoc
init_Cldif_GDP.hoc
init_Cldif_isolated_dendrite.hoc *
Isolated_Dendrite.ses *
Isolated_dendrite_Gpas.hoc
Isolated_Dendrite_PSP.ses
Isolated_Dendrite_Rin.ses
Isolated_dendrite_VDpas.hoc
start_GABA_isolated_dendrite.hoc
start_GABA_isolated_dendrite_Var_gPas.hoc
                            
COMMENT

Synaptic GABAergic mechanism

Reversal potential Egaba is changing according to [Cl-]i change (due to Cl- influx, which we hypothesize to be significant). Bicarbonate (HCO3) flows through the GABAR too, and therefore Egaba is also [HCO3]i/[HCO3]o -dependent
igaba = icl + ihco3 (we assume icl and ihco3 to be mutually independent)

Two state kinetic scheme synapse described by rise time tau1,
and decay time constant tau2. The normalized peak condunductance is 1.
Decay time MUST be greater than rise time.

The solution of A->G->bath with rate constants 1/tau1 and 1/tau2 is
 A = a*exp(-t/tau1) and
 G = a*tau2/(tau2-tau1)*(-exp(-t/tau1) + exp(-t/tau2))
	where tau1 < tau2

If tau2-tau1 -> 0 then we have a alphasynapse.
and if tau1 -> 0 then we have just single exponential decay.

The factor is evaluated in the
initial block such that an event of weight 1 generates a
peak conductance of 1.

Because the solution is a sum of exponentials, the
coupled equations can be solved as a pair of independent equations
by the more efficient cnexp method.

ENDCOMMENT


TITLE GABAergic conductance with changing Cl- concentration

NEURON {
	POINT_PROCESS gaba

	USEION cl READ ecl WRITE icl VALENCE -1
        USEION hco3 READ ehco3 WRITE ihco3 VALENCE -1

	RANGE tau1, tau2, g
	RANGE P, i

	RANGE icl, ihco3, ehco3, e
	GLOBAL total
}

UNITS {
	(mA)    = (milliamp)
	(nA)    = (nanoamp)
	(mV)    = (millivolt)
	(uS)  = (micromho)
	(mM)    = (milli/liter)
	F = (faraday) (coulombs)
	R = (k-mole)  (joule/degC)
}

PARAMETER {
	tau1	=.1	(ms)	<1e-9,1e9>
	tau2	= 80	(ms)	<1e-9,1e9>

	P       = 0.18		: HCO3/Cl relative permeability

	celsius = 31    (degC)
}

ASSIGNED {
	v	(mV)		: postsynaptic voltage

	icl	(nA)		: chloride current = 1/(1+P)*g*(v - ecl)
	ihco3	(nA)		: bicarb current = P/(1+P)*g*(v - ehco3)
	i	(nA)		: total current generated by this mechanism
				: = icl + ihco3
	g 	(uS)		: total conductance, split between bicarb (P/(1+P)*g)
				: and chloride (1/(1+P)*g)
	factor
	total	(uS)

	ecl	(mV)		: equilibrium potential for Cl-
	ehco3	(mV)		: equilibrium potential for HCO3-

	e	(mV)		: reversal potential for GABAR
}

STATE {
	A (uS)
	B (uS)
}

INITIAL {
	LOCAL tp
	total = 0
	if (tau1/tau2 > .9999) {
		tau1 = .9999*tau2
	}
	A = 0
	B = 0
	tp = (tau1*tau2)/(tau2 - tau1) * log(tau2/tau1)
	factor = -exp(-tp/tau1) + exp(-tp/tau2)
	factor = 1/factor
	e = P/(1+P)*ehco3 + 1/(1+P)*ecl
}

BREAKPOINT {
	SOLVE state METHOD cnexp

	g = B - A

	icl = 1/(1+P)*g*(v-ecl)

	ihco3 = P/(1+P)*g*(v-ehco3)
	i = icl + ihco3
	e = P/(1+P)*ehco3 + P/(1+P)*ecl

}

DERIVATIVE state {
	A' = -A/tau1
	B' = -B/tau2
}

NET_RECEIVE(weight (uS)) {
	A = A + weight*factor
	B = B + weight*factor
	total = total+weight
}

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