title: Paranodal axoglial junction is required for the maintenance of the Nav1.6-type sodium channel in the node of Ranvier in the optic nerves but not in peripheral nerve fibers in the sulfatide-deficient mice.
abstract: In myelinated axons, voltage-gated sodium channels specifically cluster at the nodes of Ranvier, while voltage-gated potassium channels are located at the juxtaparanodes. These characteristic localizations are influenced by myelination. During development, Nav1.2 first appears in the predicted nodes during myelination, and Nav1.6 replaces it in the mature nodes. Such replacements may be important physiologically. We examined the influence of the paranodal junction on switching of sodium channel subunits using the sulfatide-deficient mouse. This mutant displayed disruption of paranodal axoglial junctions and altered nodal lengths and channel distributions. The initial switching of Nav1.2 to Nav1.6 occurred in the mutant optic nerves; however, the number of Nav1.2-positive clusters was significantly higher than in wild-type mice. Although no signs of demyelination were observed at least up to 36 weeks of age, sodium channel clusters decreased markedly with age. Interestingly, Nav1.2 stayed in some of the nodal regions, especially where the nodal lengths were elongated, while Nav1.6 tended to remain in the normal-length nodes. The results in the mutant optic nerves suggested that paranodal junction formation may be necessary for complete replacement of nodal Nav1.2 to Nav1.6 during development as well as maintenance of Nav1.6 clusters at the nodes. Such subtype abnormality was not observed in the sciatic nerve, where paranodal disruption was observed. Thus, the paranodal junction significantly influences the retention of Nav1.6 in the node, which is followed by disorganization of nodal structures. However, its importance may differ between the central and peripheral nervous system.
authors.affiliation: Department of Molecular Neurobiology, School of Pharmacy, Tokyo University of Pharmacy and Life Science, Hachioji, Japan.
authors.forename: Ayaka
authors.initials: A
authors.lastname: Suzuki
authors.forename: Tomiko
authors.initials: T
authors.lastname: Hoshi
authors.forename: Tomoko
authors.initials: T
authors.lastname: Ishibashi
authors.forename: Akiko
authors.initials: A
authors.lastname: Hayashi
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Yamaguchi
authors.forename: Hiroko
authors.initials: H
authors.lastname: Baba
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001369:Axons / Q000378:metabolism*; D002553:Cerebroside-Sulfatase / Q000172:deficiency* / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D062557:NAV1.6 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism*; D009900:Optic Nerve / Q000166:cytology / Q000378:metabolism; D010525:Peripheral Nerves / Q000166:cytology / Q000378:metabolism; D011901:Ranvier's Nodes / Q000235:genetics / Q000378:metabolism*; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*; D013433:Sulfoglycosphingolipids / Q000378:metabolism
chemical_list: D062557:NAV1.6 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C491046:Scn8a protein, mouse; D015222:Sodium Channels; D013433:Sulfoglycosphingolipids; D002553:Cerebroside-Sulfatase