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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.
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
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Neuron or other electrically excitable cell;
I Cl, leak;
I Na, leak;
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I Cl, leak
I Na, leak
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