Nodes, paranodes, and incisures: from form to function.

The exquisite molecular architecture of myelinated fibers is the basis for saltatory conduction. The nodal axolemma contains high concentrations of voltage-dependent sodium channels as well as the cell adhesion molecules neurofascin and Nr-CAM, all of which are probably linked to the axonal cytoskeleton by ankyrin. At paranodes, the axonal membrane contains paranodin/Caspr, which may be a Ca(2+)-dependent cell adhesion molecule with a heterophilic partner on the apposed glial cell membrane. The juxtaparanodal axonal membrane contains the potassium channels Kv1.1 and Kv1.2, as well as the associated beta 2 subunit, which together may function to dampen re-entrant excitation. The paranodes and incisures of the Schwann cell myelin sheath contain "reflexive" adherens junctions and gap junctions. The adherens junctions are composed of E-cadherin as well as alpha- and beta-catenin, which together probably join the adjacent layers of noncompact myelin together. Reflexive gap junctions, comprising connexin32 and at least one other connexin protein, form a radial pathway for the diffusion of ions and small molecules directly across the myelin sheath.