Cytoskeletal scaffolding of Nas and Ks in neocortical pyramidal neurons: Implications for neuronal signaling and plasticity.

The initiation and propagation of action potentials (APs) depend on the precise localization of voltage-gated sodium (Na) and potassium (K) channels in neurons. In neocortical pyramidal neurons, Na1.2 and Na1.6 are key at the axon initial segment (AIS) and nodes of Ranvier (noR), driving AP initiation and propagation. Na1.2 also supports AP backpropagation in the soma and dendrites. Ankyrin-G anchors these channels at the AIS and noR, while new findings reveal that ankyrin-B scaffolds Na1.2 in dendrites. This review highlights how ankyrins stabilize Na and K channels across neuronal domains, ensuring proper function crucial for excitability, synaptic plasticity, and signaling. Recent findings explore how ankyrins differentially localize Na1.2 and Na1.6, with implications for understanding neurological disorders linked to disrupted channel localization.