Hyperexcitability from Nav1.2 channel loss in neocortical pyramidal cells (Spratt et al 2021)

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Accession:267067
Based on the Layer 5 thick-tufted pyramidal cell from the Blue Brain Project, we modify the distribution of the sodium channel Nav1.2 to recapitulate an increase in excitability observed in ex vivo slice experiments.
Reference:
1 . Spratt PWE, Alexander RPD, Ben-Shalom R, Sahagun A, Kyoung H, Keeshen CM, Sanders SJ, Bender KJ (2021) Paradoxical hyperexcitability from NaV1.2 sodium channel loss in neocortical pyramidal cells Cell Rep. 36(5):109483 [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: Prefrontal cortex (PFC);
Cell Type(s): Neocortex layer 5 pyramidal cell;
Channel(s): I h; I M; I Potassium; I Sodium; I L high threshold; I T low threshold;
Gap Junctions:
Receptor(s):
Gene(s): Nav1.2 SCN2A;
Transmitter(s):
Simulation Environment: NEURON; Python;
Model Concept(s):
Implementer(s): Ben-Shalom, Roy [rbenshalom at ucdavis.edu]; Kyoung, Henry [hkyoung at berkeley.edu];
Search NeuronDB for information about:  I L high threshold; I T low threshold; I M; I h; I Sodium; I Potassium;
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SprattEtAl2021
Ri Increase
mechanisms
branching.mod *
Ca_HVA.mod *
Ca_LVAst.mod *
CaDynamics_E2.mod
Ih.mod *
Im.mod *
K_Pst.mod *
K_Tst.mod *
na12.mod
na12_mut.mod
na1216.mod *
na1216_mut.mod *
na16.mod
na8st.mod *
Nap_Et2.mod *
NaTa_t.mod *
NaTs2_t.mod *
nax8st.mod *
ProbAMPANMDA_EMS.mod *
ProbGABAAB_EMS.mod *
SK_E2.mod *
SKv3_1.mod *
vclmp_pl.mod *
26412.tmp *
                            
:Comment : LVA ca channel. Note: mtau is an approximation from the plots
:Reference : :		Avery and Johnston 1996, tau from Randall 1997
:Comment: shifted by -10 mv to correct for junction potential
:Comment: corrected rates using q10 = 2.3, target temperature 34, orginal 21

NEURON	{
	SUFFIX Ca_LVAst
	USEION ca READ eca WRITE ica
	RANGE gCa_LVAstbar, gCa_LVAst, ica
}

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

PARAMETER	{
	gCa_LVAstbar = 0.00001 (S/cm2)
}

ASSIGNED	{
	v	(mV)
	eca	(mV)
	ica	(mA/cm2)
	gCa_LVAst	(S/cm2)
	mInf
	mTau
	hInf
	hTau
}

STATE	{
	m
	h
}

BREAKPOINT	{
	SOLVE states METHOD cnexp
	gCa_LVAst = gCa_LVAstbar*m*m*h
	ica = gCa_LVAst*(v-eca)
}

DERIVATIVE states	{
	rates()
	m' = (mInf-m)/mTau
	h' = (hInf-h)/hTau
}

INITIAL{
	rates()
	m = mInf
	h = hInf
}

PROCEDURE rates(){
  LOCAL qt
  qt = 2.3^((34-21)/10)

	UNITSOFF
		v = v + 10
		mInf = 1.0000/(1+ exp((v - -30.000)/-6))
		mTau = (5.0000 + 20.0000/(1+exp((v - -25.000)/5)))/qt
		hInf = 1.0000/(1+ exp((v - -80.000)/6.4))
		hTau = (20.0000 + 50.0000/(1+exp((v - -40.000)/7)))/qt
		v = v - 10
	UNITSON
}