Axon initial segment dysfunction in epilepsy.
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.
Wimmer
Verena C
VC
Florey Neuroscience Institutes, University of Melbourne, Parkville 3010, Victoria, Australia.
Reid
Christopher A
CA
So
Eva Y-W
EY
Berkovic
Samuel F
SF
Petrou
Steven
S
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
C484841:GABRA2 protein, human; D007473:Ion Channels; D011963:Receptors, GABA-A; D015222:Sodium Channels