A Review of Systems Biology of Axon Initial Segment: Action Potential Initiation, Propagation, and Neurological Diseases

The axon initial segment (AIS) region is crucial for action potential (AP) initiation due to its molecular organization especially voltage gated ion channels and Ankyrin-G (AnkG). AnkG act as recruiter and restrict almost all the proteins at AIS in order to maintain the AIS assembly. Voltage gated sodium channels (Nav channels) are enriched at AIS with high density and independently responsible for the AP initiation. Moreover, AIS also contains voltage gated potassium channels (Kv channels) for repolarization phase of AP, microtubules (MTs) responsible for the proper protein trafficking through molecular motors. AIS also acts as a cytoplasmic filter and diffusion barrier, responsible for the selective entry of the proteins into axon. Mutation of AIS related protein can cause various neurological dysfunction including Alzheimer’s disease. This review also reflects the role and importance of computational modelling in the understanding of action potential mechanisms mathematically.