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Controlling the precise density and distribution of voltage-gated ion channels at the AIS could be achieved by fine regulation of membrane trafficking. We speculate that the coordinated membrane insertion and internalization and controlled diffusion might be pivotal in altering the AIS composition in ion channels during plasticity. We envision some control mechanisms, focusing on PTM, such as phosphorylation/dephosphorylation, which control the shuttling of Kv1 between microtubules and the plasma membrane, as well as the membrane stability of Nav1, Kv7, and NFasc through their anchoring to AnkG. Moreover, palmitoylation of PSD-93 influences its AIS accumulation as well as the AIS density of its associated channels Kv1.1, Kv1.2, and Kv1.4.

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