Fig. 1

Excitable domains along the myelinated nerve fiber. a Cartoon illustrating the structures of the myelinated nerve fiber and excitable axonal domains: axon initial segment (AIS) and nodes of Ranvier. b Schematic presentation showing molecular mechanisms of AIS formation. Intra-axonal boundary between the AIS and distal axon is formed by submembranous cytoskeletal complexes, ankyrinG-βIV spectrin in the AIS and ankyrinB-αII/βII spectrins in the distal axon. c Schematic presentation showing molecular mechanisms of node of Ranvier formation. Paranodal junctions formed by cell adhesion molecules, axonal contactin and contactin-associated protein (Caspr), and glial neurofascin (NF) 155 act as a diffusion barrier to restrict the mobility of nodal and juxtaparanodal molecules. Nodal protein complex is secured by the interaction between the axonal cell adhesion molecule NF186 and extracellular matrix molecules such as brevican. An ankyrinG-βIV spectrin complex links Nav channels to the actin cytoskeleton to further stabilize Nav channel complex. d Cultured hippocampal neurons. Antibody to neurofascin shows AIS (red), whereas antibody to MAP2 showes somatodendritic domains (green). Scale bar 20 μm. e Longitudinal section of mouse optic nerve. Nav channels at nodes (red) and voltage-gated potassium (Kv) 1.2 channels at juxtaparanodes (green). Scale bar 5 μm (color figure online)