Abstract
The initiation and propagation of action potentials (APs) depend on the precise localization of voltage-gated sodium (Na(V)) and potassium (K(V)) channels in neurons. In neocortical pyramidal neurons, Na(V)1.2 and Na(V)1.6 are key at the axon initial segment (AIS) and nodes of Ranvier (noR), driving AP initiation and propagation. Na(V)1.2 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 Na(V)1.2 in dendrites. This review highlights how ankyrins stabilize Na(V) and K(V) channels across neuronal domains, ensuring proper function crucial for excitability, synaptic plasticity, and signaling. Recent findings explore how ankyrins differentially localize Na(V)1.2 and Na(V)1.6, with implications for understanding neurological disorders linked to disrupted channel localization.