title: Axon initial segment dysfunction in epilepsy.
abstract: The axon initial segment (AIS) contains the site of action potential initiation and plays a major role in neuronal excitability. AIS function relies on high concentrations of different ion channels and complex regulatory mechanisms that orchestrate molecular microarchitecture. We review recent evidence that a large number of ion channels associated with epilepsy are enriched at the AIS, making it a 'hotspot' for epileptogenesis. Furthermore, we present novel data on the clustering of GABRgamma2 receptors in the AIS of cortical and hippocampal neurons in a knock in mouse model of a human genetic epilepsy. This article highlights the molecular coincidence of epilepsy mutations at the AIS and reviews pathogenic mechanisms converging at the AIS.
authors.affiliation: Florey Neuroscience Institutes, University of Melbourne, Parkville 3010, Victoria, Australia.
authors.forename: Verena C
authors.initials: VC
authors.lastname: Wimmer
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Reid
authors.forename: Eva Y-W
authors.initials: EY
authors.lastname: So
authors.forename: Samuel F
authors.initials: SF
authors.lastname: Berkovic
authors.forename: Steven
authors.initials: S
authors.lastname: Petrou
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001369:Axons / Q000737:chemistry / Q000502:physiology*; D003627:Data Interpretation, Statistical; D004594:Electrophysiology; D004827:Epilepsy / Q000503:physiopathology*; D018014:Gene Transfer Techniques; D006801:Humans; D007473:Ion Channels / Q000235:genetics / Q000502:physiology*; D018613:Microscopy, Confocal; D011963:Receptors, GABA-A / Q000235:genetics / Q000502:physiology; D015222:Sodium Channels / Q000235:genetics / Q000502:physiology; D016707:Tissue Fixation
chemical_list: C484841:GABRA2 protein, human; D007473:Ion Channels; D011963:Receptors, GABA-A; D015222:Sodium Channels