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.
Model Type: Neuron or other electrically excitable cell
Currents: I K; I Na,t; I_AHP; KCC2; NKCC1; I K,leak; I Cl, leak; I Na, leak; I Na,p; Na/K pump
Genes: Nav1.1 SCN1A
Model Concept(s): Spreading depolarization; Epilepsy
Simulation Environment: XPPAUT
References:
Lemaire L et al. (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)