Faculty Opinions recommendation of Paranodal interactions regulate expression of sodium channel subtypes and provide a diffusion barrier for the node of Ranvier.

To ensure rapid and efficient impulse conduction, myelinated axons establish and maintain specific protein domains. For instance, sodium (Na+) channels accumulate in the node of Ranvier; potassium (K+) channels aggregate in the juxtaparanode and neurexin/caspr/paranodin clusters in the paranode. Our understanding of the mechanisms that control the initial clustering of these proteins is limited and less is known about domain maintenance. Correlative data indicate that myelin formation and/or mature myelin-forming cells mediate formation of all three domains. Here, we test whether myelin is required for maintaining Na+ channel domains in the nodal gap by employing two demyelinating murine models: (1) cuprizone ingestion, which induces complete demyelination through oligodendrocyte toxicity; and (2) ceramide galactosyltransferase deficient mice, which undergo spontaneous adult-onset demyelination without oligodendrocyte death. Our data indicate that the myelin sheath is essential for long-term maintenance of sodium channel domains; however, oligodendrocytes, independent of myelin, provide a partial protective influence on the maintenance of nodal Na+ channel clusters. Thus, we propose that multiple mechanisms regulate the maintenance of nodal protein organization. Finally, we present evidence that following the loss of Na+ channel clusters the chronological progression of expression and reclustering of Na+ channel isoforms during the course of CNS remyelination recapitulates development.

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Nr-CAM and neurofascin interactions regulate ankyrin G and sodium channel clustering at the node of Ranvier

Current Biology ◽

10.1016/s0960-9822(01)00586-3 ◽

2001 ◽

Vol 11 (23) ◽

pp. 1864-1869 ◽

Cited By ~ 48

Author(s):

M. Lustig ◽

G. Zanazzi ◽

T. Sakurai ◽

C. Blanco ◽

S.R. Levinson ◽

...

Keyword(s):

Sodium Channel ◽

Node Of Ranvier ◽

Ankyrin G ◽

Sodium Channel Clustering

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Faculty Opinions recommendation of Nr-CAM and neurofascin interactions regulate ankyrin G and sodium channel clustering at the node of Ranvier.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1002950.30861 ◽

2001 ◽

Author(s):

Vance Lemmon

Keyword(s):

Sodium Channel ◽

Node Of Ranvier ◽

Ankyrin G ◽

Sodium Channel Clustering

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The reaction between tetrodotoxin and membrane sites at the node of Ranvier: its kinetics and dependence on pH

Philosophical Transactions of the Royal Society of London Series B Biological Sciences ◽

10.1098/rstb.1975.0015 ◽

1975 ◽

Vol 270 (908) ◽

pp. 353-363 ◽

Cited By ~ 9

Keyword(s):

Membrane Potential ◽

Sodium Channel ◽

Dissociation Constant ◽

Voltage Clamp ◽

Room Temperature ◽

Node Of Ranvier ◽

Low Ph ◽

Equilibrium Dissociation Constant ◽

Sodium Permeability ◽

Equilibrium Dissociation

Voltage clamp experiments were done on single nodes of Ranvier to study the inhibition of the sodium permeability by tetrodotoxin (TTX). Equilibrium results could be excellently fitted on the assumption that a sodium channel is blocked when one toxin molecule binds to it, the equilibrium dissociation constant, K T of this reaction being 3.6 nM at 20 °G. Onset and offset of block could be quantitatively interpreted to be determined by the rates of the TTX-channel reaction whose average constants, at room temperature, were 3 x 10 6 m -1 s -1 for the association (k 1 ) and 1.4 x 10 -2 s -1 for the dissociation (k 2 ). The dependence of the constants on temperature could be described by Arrhenius plots yielding activation energies of 29.3, 85.5 and 41.0 (57.3) kJ/mol for K T , k 2 and k 1 (k 1 derived from onset alone), respectively. At low pH the relative TTX effect was clearly less than at neutral pH. These results could be explained by a model involving the competition of TTX and protons for the same’receptor to which protons bind as a function of membrane potential.

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Immuno-ultrastructural localization of sodium channels at nodes of Ranvier and perinodal astrocytes in rat optic nerve

Proceedings of the Royal Society of London Series B Biological Sciences ◽

10.1098/rspb.1989.0065 ◽

1989 ◽

Vol 238 (1290) ◽

pp. 39-51 ◽

Cited By ~ 45

Keyword(s):

Optic Nerve ◽

Sodium Channel ◽

Sodium Channels ◽

Node Of Ranvier ◽

Ultrastructural Localization ◽

Active Role ◽

Nodes Of Ranvier ◽

Electron Microscopic ◽

Axon Membrane ◽

Intense Immunoreactivity

Immuno-electron microscopic localization of sodium channels at nodes of Ranvier within adult optic nerve was demonstrated with polyclonal antibody 7493. The 7493 antisera, which is directed against purified sodium channels from rat brain, recognizes a 260 kDa protein in immunoblots of the crude glycoprotein fraction from adult rat optic nerve. Intense immunoreactivity with 7493 antisera was observed at nodes of Ranvier. Axon membrane at the node was densely stained, whereas paranodal and internodal axon membrane did not exhibit immunoreactivity. The axoplasm beneath the nodal membrane displayed variable immunostaining. Neither terminal paranodal oligodendroglial loops nor oligodendrocyte plasmalemma were immunoreactive with 7493 antisera. However, perinodal astrocyte processes exhibited intense immunoreactivity with the anti-sodium channel antisera. Optic nerves incubated with pre-immune sera, or with 7493 antisera that had been pre-adsorbed with purified sodium channel protein, displayed no immunoreactivity. These results demonstrate localization of sodium channels at high density at mammalian nodes of Ranvier and in some perinodal astrocyte processes. The latter observation offers support for an active role for perinodal astrocyte processes in the aggregation of sodium channels within the axon membrane at the node of Ranvier.

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