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]
Citations  Citation Browser
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
Na12 Analysis
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 : The persistent component of the K current
:Reference : :		Voltage-gated K+ channels in layer 5 neocortical pyramidal neurones from young rats:subtypes and gradients,Korngreen and Sakmann, J. Physiology, 2000
:Comment : shifted -10 mv to correct for junction potential
:Comment: corrected rates using q10 = 2.3, target temperature 34, orginal 21


NEURON	{
	SUFFIX K_Pst
	USEION k READ ek WRITE ik
	RANGE gK_Pstbar, gK_Pst, ik
}

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

PARAMETER	{
	gK_Pstbar = 0.00001 (S/cm2)
}

ASSIGNED	{
	v	(mV)
	ek	(mV)
	ik	(mA/cm2)
	gK_Pst	(S/cm2)
	mInf
	mTau
	hInf
	hTau
}

STATE	{
	m
	h
}

BREAKPOINT	{
	SOLVE states METHOD cnexp
	gK_Pst = gK_Pstbar*m*m*h
	ik = gK_Pst*(v-ek)
}

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/(1 + exp(-(v+1)/12)))
        if(v<-50){
		    mTau =  (1.25+175.03*exp(-v * -0.026))/qt
        }else{
            mTau = ((1.25+13*exp(-v*0.026)))/qt
        }
		hInf =  1/(1 + exp(-(v+54)/-11))
		hTau =  (360+(1010+24*(v+55))*exp(-((v+75)/48)^2))/qt
		v = v - 10
	UNITSON
}