Figure 2:

Developmental reorganization of Na_v1.2 channels contributes to distinct functions at different stages of neuronal maturation. In immature neurons (left), Na_v1.2 channels decorate the axon initial segment (AIS) and entire length of the axon, underpinning their indispensable role in action potential generation and propagation at early postnatal ages. In mature neurons (right), Na_v1.2 channels display somatodendritic localization and are restricted to the proximal AIS. They are replaced in the distal AIS and Nodes of Ranvier by Na_v1.6 channels. As a consequence of this dynamic subcellular regulation of channel distribution, Scn2a inactivation yields distinct electrophysiological phenotypes in immature and mature cortical projection neurons, and SCN2A loss-of-function variants preferentially affect immature neuron excitability.