Modeling protein-protein interactions in axon initial segment to understand their potential impact on action potential initiation

The axon initial segment (AIS) region is crucial for action potential initiation due to the presence of high-density AIS protein voltage-gated sodium channels (Na(v)). Na(v) channels comprise several serine residues responsible for the recruitment of Na(v) channels into the structure of AIS through interactions with ankyrin-G (AnkG). In this study, a series of computational experiments are performed to understand the role of AIS proteins casein kinase 2 and AnkG on Na(v) channel recruitment into the AIS. The computational simulation results using Virtual cell software indicate that Na(v) channels with all serine sites available for phosphorylation bind to AnkG with strong affinity. At the low initial concentration of AnkG and casein kinase 2, the concentration of Na(v) channels reduces significantly, suggesting the importance of casein kinase 2 and AnkG in the recruitment of Na(v) channels.