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 *
                            
: SK-type calcium-activated potassium current
: Reference : Kohler et al. 1996

NEURON {
       SUFFIX SK_E2
       USEION k READ ek WRITE ik
       USEION ca READ cai
       RANGE gSK_E2bar, gSK_E2, ik
}

UNITS {
      (mV) = (millivolt)
      (mA) = (milliamp)
      (mM) = (milli/liter)
}

PARAMETER {
          v            (mV)
          gSK_E2bar = .000001 (mho/cm2)
          zTau = 1              (ms)
          ek           (mV)
          cai          (mM)
}

ASSIGNED {
         zInf
         ik            (mA/cm2)
         gSK_E2	       (S/cm2)
}

STATE {
      z   FROM 0 TO 1
}

BREAKPOINT {
           SOLVE states METHOD cnexp
           gSK_E2  = gSK_E2bar * z
           ik   =  gSK_E2 * (v - ek)
}

DERIVATIVE states {
        rates(cai)
        z' = (zInf - z) / zTau
}

PROCEDURE rates(ca(mM)) {
          if(ca < 1e-7){
	              ca = ca + 1e-07
          }
          zInf = 1/(1 + (0.00043 / ca)^4.8)
}

INITIAL {
        rates(cai)
        z = zInf
}