Axon initial segment dysfunction in epilepsy

作者：Wimmer Verena C; Reid Christopher A; So Eva Y W; Berkovic Samuel F; Petrou Steven^*

来源：The Journal of Physiology, 2010, 588(11): 1829-1840.

DOI：10.1113/jphysiol.2010.188417

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 GABR gamma 2 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.

• 出版日期2010-6-1