Two-neuron conductance-based model with dynamic ion concentrations to study NaV1.1 channel mutations

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Gain of function mutations of SCN1A, the gene coding for the voltage-gated sodium channel NaV1.1, cause familial hemiplegic migraine type 3 (FHM-3), whereas loss of function mutations cause different types of epilepsy. To study those mutations, we developed a two-neuron conductance-based model of interconnected GABAergic and pyramidal glutamatergic neurons, with dynamic ion concentrations. We modeled FHM-3 mutations with persistent sodium current in the GABAergic neuron and epileptogenic mutations by decreasing the fast-inactivating sodium conductance in the GABAergic neuron.
1 . Lemaire L, Desroches M, Krupa M, Pizzamiglio L, Scalmani P, Mantegazza M (2021) Modeling NaV1.1/SCN1A sodium channel mutations in a microcircuit with realistic ion concentration dynamics suggests differential GABAergic mechanisms leading to hyperexcitability in epilepsy and hemiplegic migraine PLoS Computational Biology 17(7):e1009239
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):
Channel(s): I K; I Na,t; I_AHP; KCC2; NKCC1; I K,leak; I Cl, leak; I Na, leak; I Na,p; Na/K pump;
Gap Junctions:
Receptor(s): GabaA; AMPA;
Gene(s): Nav1.1 SCN1A;
Transmitter(s): Gaba; Glutamate;
Simulation Environment: XPP;
Model Concept(s): Spreading depolarization; Epilepsy;
Search NeuronDB for information about:  GabaA; AMPA; I Na,p; I Na,t; I K; I K,leak; Na/K pump; I_AHP; I Cl, leak; I Na, leak; KCC2; NKCC1; Gaba; Glutamate;
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