Initiation of spreading depolarization by GABAergic neuron hyperactivity & NaV 1.1 (Chever et al 21)

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Accession:267157
Experimentally, we show that acute pharmacological activation of NaV1.1 (the main Na+ channel of interneurons) or optogenetic-induced hyperactivity of GABAergic interneurons is sufficient to ignite CSD in the neocortex by spiking-generated extracellular K+ build-up. Neither GABAergic nor glutamatergic synaptic transmission were required for CSD initiation. CSD was not generated in other brain areas, suggesting that this is a neocortex-specific mechanism of CSD initiation. Gain-of-function mutations of NaV1.1 (SCN1A) cause Familial Hemiplegic Migraine type-3 (FHM3), a subtype of migraine with aura, of which CSD is the neurophysiological correlate. Our results provide the mechanism linking NaV1.1 gain-of-function to CSD generation in FHM3. Those findings are supported by the two-neuron conductance-based model with dynamic ion concentrations we developed.
Reference:
1 . Chever O, Zerimech S, Scalmani P, Lemaire L, Pizzamiglio L, Loucif A, Ayrault M, Krupa M, Desroches M, Duprat F, Léna I, Cestèle S, Mantegazza M (2021) Initiation of migraine-related cortical spreading depolarization by hyperactivity of GABAergic neurons and NaV1.1 channels J Clin Invest. [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Neuron or other electrically excitable cell; Extracellular;
Brain Region(s)/Organism:
Cell Type(s):
Channel(s): I Na,p; I K; I Cl, leak; I K,leak; I Na, leak; Na/K pump; I Na,t; NKCC1; KCC2; I_AHP;
Gap Junctions:
Receptor(s): GabaA; AMPA;
Gene(s): Nav1.1 SCN1A;
Transmitter(s): Glutamate; Gaba;
Simulation Environment: XPP;
Model Concept(s): Spreading depolarization; Dynamic extracellular concentrations;
Implementer(s):
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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2_neurons_NaV1_1
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