Pleiotropic effects of SCZ-associated genes (Mäki-Marttunen et al. 2017)

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Accession:187615
Python and MATLAB scripts for studying the dual effects of SCZ-related genes on layer 5 pyramidal cell firing and sinoatrial node cell pacemaking properties. The study is based on two L5PC models (Hay et al. 2011, Almog & Korngreen 2014) and SANC models (Kharche et al. 2011, Severi et al. 2012).
Reference:
1 . Mäki-Marttunen T, Lines GT, Edwards AG, Tveito A, Dale AM, Einevoll GT, Andreassen OA (2017) Pleiotropic effects of schizophrenia-associated genetic variants in neuron firing and cardiac pacemaking revealed by computational modeling. Transl Psychiatry 7:5 [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:
Cell Type(s): Neocortex L5/6 pyramidal GLU cell; Cardiac atrial cell;
Channel(s): I Na,p; I Na,t; I L high threshold; I T low threshold; I A; I K; I M; I h; I K,Ca; I Sodium; I Calcium; I Potassium; I A, slow; Na/Ca exchanger; I_SERCA; Na/K pump; Kir;
Gap Junctions:
Receptor(s):
Gene(s): Nav1.1 SCN1A; Cav3.3 CACNA1I; Cav1.3 CACNA1D; Cav1.2 CACNA1C;
Transmitter(s):
Simulation Environment: NEURON; MATLAB; Python;
Model Concept(s): Schizophrenia;
Implementer(s): Maki-Marttunen, Tuomo [tuomomm at uio.no];
Search NeuronDB for information about:  Neocortex L5/6 pyramidal GLU cell; I Na,p; I Na,t; I L high threshold; I T low threshold; I A; I K; I M; I h; I K,Ca; I Sodium; I Calcium; I Potassium; I A, slow; Na/Ca exchanger; I_SERCA; Na/K pump; Kir;
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pleiotropy
hay
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fig1_curves.mat
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mutation_stuff.py *
mytools.py *
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scalings_cs.sav
                            
: 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, offc, zTau, sloc
}

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

PARAMETER {
          v            (mV)
          gSK_E2bar = .000001 (mho/cm2)
          zTau = 1              (ms)
          ek           (mV)
          cai          (mM)
          offc = 0.00043 (mM)
	  sloc = 4.8
}

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 + (offc / ca)^sloc)
}

INITIAL {
        rates(cai)
        z = zInf
}