Cytoskeletal scaffolding of NaVs and KVs in neocortical pyramidal neurons: Implications for neuronal signaling and plasticity

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_V1.2 and Na_V1.6 are key at the axon initial segment (AIS) and nodes of Ranvier (noR), driving AP initiation and propagation. Na_V1.2 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_V1.2 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_V1.2 and Na_V1.6, with implications for understanding neurological disorders linked to disrupted channel localization.