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 *
                            
: Dynamics that track inside calcium concentration
: modified from Destexhe et al. 1994

NEURON	{
	SUFFIX CaDynamics_E2
	USEION ca READ ica WRITE cai
	RANGE decay, gamma, minCai, depth, ica
}

UNITS	{
	(mV) = (millivolt)
	(mA) = (milliamp)
	FARADAY = (faraday) (coulombs)
	(molar) = (1/liter)
	(mM) = (millimolar)
	(um)	= (micron)
}

PARAMETER	{
	gamma = 0.05 : percent of free calcium (not buffered)
	decay = 80 (ms) : rate of removal of calcium
	depth = 0.1 (um) : depth of shell
	minCai = 1e-4 (mM)
}

ASSIGNED	{ica (mA/cm2)}

STATE	{
	cai (mM)
	}

BREAKPOINT	{ SOLVE states METHOD cnexp }

DERIVATIVE states	{
	cai' = -(10000)*(ica*gamma/(2*FARADAY*depth)) - (cai - minCai)/decay
}