nodeparanode

Nodeparanode is a term used to describe the functional unit formed by the node of Ranvier and the surrounding paranodal regions on a myelinated axon. It denotes the close structural and functional integration that supports rapid, saltatory conduction along nerve fibers.

The node of Ranvier is characterized by a high density of voltage-gated sodium channels, such as Nav1.6, which cluster at the nodal membrane and are anchored to the cytoskeleton by proteins like ankyrin-G and βIV-spectrin. Flanking the node are the paranodes, where glial loops form septate-like junctions with the axonal membrane. Key molecular interactions include axonal Caspr1 and CNTN1 pairing with glial NF155, establishing a tight axo-glial junction that helps to insulate the node and restrict lateral diffusion of ion channels and membrane proteins.

Functionally, the nodeparanode unit supports efficient saltatory conduction by maintaining a high-resistance, low-leakage pathway for electrical signals and by organizing the localization of ion channels and cytoskeletal elements. The integrity of these regions is important for the rapid transmission of action potentials and for preserving nerve excitability.

Development and maintenance involve myelination by glial cells and the maturation of nodal and paranodal protein complexes. Disruption of nodeparanode architecture, whether by genetic mutations or autoantibody-mediated damage, can lead to conduction abnormalities and demyelinating neuropathies. Autoimmune paranodopathies targeting NF155, CNTN1, or related proteins are among clinical conditions associated with nodeparanode dysfunction.