. Cav2, 3 qui n'a qu'un effet limité et non significatif, ni celle de canaux CaV1.2 qui n'a pas d'effet du tout sur l'induction de la DCE, vol.2

R. Oliveira, obtained under a MTA from Jeff Clare, Glaxo-SmithKline, UK), which were cultured in modified Dulbecco's medium supplemented with 10 % fetal bovine serum (Invitrogen-ThermoFisher, USA). Cell cultures were tested for mycoplasma contamination, 2004.

. Bechi, Sodium currents were recorded with the wholecell configuration of the patch-clamp technique (24-48 h after transfection for NaV1.1 and NaV1.2) as previously described, 2012.

, The extracellular recording solution contained (in mM): 150 NaCl, 10 HEPES, 2 KCl, vol.1

, CaCl2 and 1 MgCl2 (pH 7.4 with CsOH); the internal pipette solution contained

, CsF, 35 NaCl, 10 EGTA, 10 HEPES

, Pharmacological agents and chemicals

. Gabazine, CNQX disodium salt, VU0240551 and VU0463271 from Tocris Bioscience (UK), CPP and TTXcitrate from Alomone labs (Israel), Isoguvacine and CdCl2 were bought from Sigma-Aldrich (USA)

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, Nous avons comparé le taux d'induction de la DCE par activation spécifique des neurones GABAergiques lors d'une perfusion d'ACSF modifié (d'enregistrement) et d'ACSF standard (de coupe et de stockage)

, La latence moyenne avant induction est 29 sec (± 12) en ACSFm (n=6) et de 45.14 sec (± 13.25) en ACSFs (n=7)

, Cholinergic activation inhibits cortical spreading depression through muscarinic receptors in acute mouse neocortical slices

, Massimo Mantegazza, vol.1, p.3

, CNRS UMR7275, Institute of Molecular and Cellular Pharmacology (IPMC)

. Inserm,

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, Rôle du NaV1.1 et des neurones GABAergiques dans l'induction de la DCE

, La forme rare et monogénique de Migraine avec aura, appelée Migraine Hémiplégique Familiale, est causée par la mutation de trois gènes bien distincts : CACNA1 (pour le canal CaV2.1), ATPA1A (pour la sous unité alpha 2 de la pompe NaK ATPase) et SCN1A

, L'étude des modèles de souris de MHF 1 (mutation gain de fonction du CaV2.1) et de MHF 2 (mutation perte de fonction de Na-K-ATPase)

, Le type 3 de MHF est du à des mutations du NaV1.1, un canal sodique dépendant du potentiel, majoritairement exprimé dans les neurones GABAergiques où ils sont très importants pour leur excitabilité, Glutamate et du Potassium dans l'initiation de la DCE

, Plusieurs études menées dans notre laboratoire ont montré sur neurones transfectés en culture qu'il s'agissait d'une mutation gain de fonction, entrainant une augmentation de l'excitabilité des neurones. Cependant, le lien entre cette mutation, l'hyperexcitabilité corticale et la facilitation de la DCE -déjà observée dans les autres modèles de FHM

, Tout d'abord, en nous basant sur la mutation gain de fonction du canal NaV1.1 qui provoque la Migraine Hémiplégique Familiale de type 3, et l'hyperexcitabilité observée dans des neurones transfectés avec le canal muté

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