Axon initial segment dysfunction in epilepsy


Corresponding author S. Petrou: Florey Neuroscience Institutes, Parkville, Victoria 3010, Australia; The University of Melbourne, Parkville 3010, Australia.  Email:


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 GABRγ2 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.