Nodes, Paranodes, and Incisures: From Form to Function.

Abstract

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 Ca2+-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 β2 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 α- and β-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.