Editing Node of Ranvier (section)

==Structure==
The internodes are the [[myelin]] segments and the gaps between are referred to as nodes.  The size and the spacing of the internodes vary with the fiber diameter in a curvilinear relationship that is optimized for maximal conduction velocity.<ref>{{cite journal | author = gxnSalzer J. L. | year = 1997 | title = Clustering sodium channels at the node of Ranvier: close encounters of the axon-glia kind | journal = [[Neuron (journal)|Neuron]] | volume = 18 | issue = 6 | pages = 843–846 | doi = 10.1016/S0896-6273(00)80323-2 | pmid = 9208851 | s2cid = 6743084 | doi-access = free }}</ref>  The size of the nodes span from 1–2&nbsp;μm whereas the internodes can be up to (and occasionally even greater than)1.5 millimetres long, depending on the axon diameter and fiber type.

The structure of the node and the flanking paranodal regions are distinct from the internodes under the compact myelin sheath, but are very similar in CNS and PNS.  The axon is exposed to the extra-cellular environment at the node and is constricted in its diameter.  The decreased axon size reflects a higher packing density of [[neurofilaments]] in this region, which are less heavily phosphorylated and are transported more slowly.<ref name="Salzer J. L.-1997">{{cite journal | author = Salzer J. L. | year = 1997 | title = Clustering sodium channels at the node of Ranvier: close encounters of the axon-glia kind | journal = [[Neuron (journal)|Neuron]] | volume = 18 | issue = 6 | pages = 843–846 | doi = 10.1016/S0896-6273(00)80323-2 | pmid = 9208851 | s2cid = 6743084 | doi-access = free }}</ref>  Vesicles and other organelles are also increased at the nodes, which suggest that there is a bottleneck of axonal transport in both directions as well as local axonal-glial signaling.

When a longitudinal section is made through a myelinating [[Schwann cell]] at the node, three distinctive segments are represented: the stereotypic [[Internodal segment|internode]], the paranodal region, and the node itself.  In the internodal region, the Schwann cell has an outer collar of cytoplasm, a compact myelin sheath, and inner collar of cytoplasm, and the axolemma.  At the paranodal regions, the paranodal cytoplasm loops contact thickenings of the axolemma to form septate –like junctions.  In the node alone, the axolemma is contacted by several Schwann microvilli and contains a dense cytoskeletal undercoating.

===Differences in the central and peripheral nervous systems===
Although [[freeze fracture]] studies have revealed that the nodal axolemma in both the CNS and PNS is enriched in intra-membranous particles (IMPs) compared to the internode, there are some structural differences reflecting their cellular constituents.<ref name="Salzer J. L.-1997" />  In the PNS, specialized microvilli project from the outer collar of Schwann cells and come very close to nodal axolemma of large fibers.  The projections of the Schwann cells are perpendicular to the node and are radiating from the central axons.  However, in the CNS, one or more of the astrocytic processes come in close vicinity of the nodes.  Researchers declare that these processes stem from multi-functional astrocytes, as opposed to from a population of astrocytes dedicated to contacting the node.  On the other hand, in the PNS, the basal lamina that surrounds the Schwann cells is continuous across the node. A study suggests that in the CNS, nerve cells individually alter the size of the nodes to tune conduction speeds, leading node length to vary much more across different axons than within one.<ref name="eLife2017">{{cite journal |last1=Arancibia-Cárcamo |first1=IL |last2=Ford |first2=MC |last3=Cossell |first3=L |last4=Ishida |first4=K |last5=Tohyama |first5=K |last6=Attwell |first6=D |title=Node of Ranvier length as a potential regulator of myelinated axon conduction speed. |journal=eLife |date=28 January 2017 |volume=6 |doi=10.7554/eLife.23329 |doi-access=free |pmid=28130923|pmc=5313058 }}</ref>

===Composition===
The nodes of Ranvier Na+/Ca2+ exchangers and high density of voltage-gated Na+ channels that generate action potentials.  A sodium channel consists of a pore-forming α subunit and two accessory β subunits, which anchor the channel to extra-cellular and intra-cellular components.  The nodes of Ranvier in the central and peripheral nervous systems mostly consist of αNaV1.6 and β1 subunits.<ref>{{cite journal | doi = 10.1016/S0896-6273(01)00266-5 | pmid = 11343648 | author1 = Kaplan M.R. | author2 = Cho M.H. | author3 = Ullian E.M. | author4 = Isom L.L. | author5 = Levinson S.R. | author6 = Barres B.A. | year = 2001 | title = Differential control of clustering of the sodium channels Na(v)1.2 and Na(v)1.6 at developing CNS nodes of Ranvier | journal = [[Neuron (journal)|Neuron]] | volume = 30 | issue = 1 | pages = 105–119 | s2cid = 10252129 | doi-access = free }}</ref> The extra-cellular region of β subunits can associate with itself and other proteins, such as tenascin R and the cell-adhesion molecules [[neurofascin]] and contactin.  Contactin is also present at nodes in the CNS and interaction with this molecule enhances the surface expression of Na+ channels.

[[Ankyrin]] has been found to be bounded to βIV spectrin, a spectrin isoform enriched at nodes of Ranvier and axon initial segments.   The PNS nodes are surrounded by Schwann cell microvilli, which contain ERMs and EBP50 that may provide a connection to actin microfilaments. Several extracellular matrix proteins are enriched at nodes of Ranvier, including [[tenascin-R]], [[HAPLN2|Bral-1]], and proteoglycan NG2, as well as [[phosphacan]] and [[versican]] V2. At CNS nodes, the axonal proteins also include contactin; however, different from the PNS, Schwann cell microvilli are replaced by [[astrocyte]] perinodal extensions.

===Molecular organization===
The molecular organization of the nodes corresponds to their specialized function in impulse propagation.  The level of sodium channels in the node versus the internode suggests that the number IMPs corresponds to sodium channels.  Potassium channels are essentially absent in the nodal axolemma, whereas they are highly concentrated in the paranodal axolemma and Schwann cell membranes at the node.<ref name="Salzer J. L.-1997" /> The exact function of potassium channels have not quite been revealed, but it is known that they may contribute to the rapid repolarization of the action potentials or play a vital role in buffering the potassium ions at the nodes.  This highly asymmetric distribution of voltage-gated sodium and potassium channels is in striking contrast to their diffuse distribution in unmyelinated fibers.<ref name="Salzer J. L.-1997" /><ref>Black, J.A., Sontheimer, H., Oh, Y., and Waxman, S.G. (1995). <u>In The Axon</u>, S. Waxman, J. Kocsis, and P. Stys, eds. [[Oxford University Press]], [[New York City|New York]], pp. 116–143.</ref>

The filamentous network subjacent to the nodal membrane contains cytoskeletal proteins called [[spectrin]] and [[ankyrin]].  The high density of ankyrin at the nodes may be functionally significant because several of the proteins that are populated at the nodes share the ability to bind to ankyrin with extremely high affinity.  All of these proteins, including ankyrin, are enriched in the initial segment of axons which suggests a functional relationship.  Now the relationship of these molecular components to the clustering of sodium channels at the nodes is still not known.  Although some cell-adhesion molecules have been reported to be present at the nodes inconsistently; however, a variety of other molecules are known to be highly populated at the glial membranes of the paranodal regions where they contribute to its organization and structural integrity.