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Axons transmit action potentials with high fidelity and minimal jitter. Thisunique capability is likely the result of the spatiotemporal arrangement ofsodium channels along the axon. Super-resolution microscopy recently revealedthat the axon membrane skeleton is structured as a series of actin ringsconnected by spectrin filaments that are held under entropic tension. Sodiumchannels also exhibit a periodic distribution pattern, as they bind to ankyrinG, which associates with spectrin. Here, we elucidate the relationship betweenthe axon membrane skeleton structure and the function of the axon. By combiningcytoskeletal dynamics and continuum diffusion modeling, we show that spectrinfilaments under tension minimize the thermal fluctuations of sodium channelsand prevent overlap of neighboring channel trajectories. Importantly, this axonskeletal arrangement allows for a highly reproducible band-like activation ofsodium channels leading to coordinated sodium propagation along the axon.

Axon Membrane Skeleton Structure is Optimized for Coordinated Sodium Propagation