title: Aging-associated changes in motor axon voltage-gated Na(+) channel function in mice.
abstract: Accumulating myelin abnormalities and conduction slowing occur in peripheral nerves during aging. In mice deficient of myelin protein P0, severe peripheral nervous system myelin damage is associated with ectopic expression of Nav1.8 voltage-gated Na(+) channels on motor axons aggravating the functional impairment. The aim of the present study was to investigate the effect of regular aging on motor axon function with particular emphasis on Nav1.8. We compared tibial nerve conduction and excitability measures by threshold tracking in 12 months (mature) and 20 months (aged) wild-type (WT) mice. With aging, deviations during threshold electrotonus were attenuated and the resting current-threshold slope and early refractoriness were increased. Modeling indicated that, in addition to changes in passive membrane properties, motor fibers in aged WT mice were depolarized. An increased Nav1.8 isoform expression was found by immunohistochemistry. The depolarizing excitability features were absent in Nav1.8 null mice, and they were counteracted in WT mice by a Nav1.8 blocker. Our data suggest that alteration in voltage-gated Na(+) channel isoform expression contributes to changes in motor axon function during aging.
authors.affiliation: Department of Neuroscience and Pharmacology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Neurophysiology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Mihai
authors.initials: M
authors.lastname: Moldovan
authors.affiliation: Department of Neuroscience and Pharmacology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Mette Romer
authors.initials: MR
authors.lastname: Rosberg
authors.affiliation: Department of Neuroscience and Pharmacology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Susana
authors.initials: S
authors.lastname: Alvarez
authors.affiliation: Department of Neurology, Developmental Neurobiology, University of Würzburg, Wurzburg, Germany.
authors.forename: Dennis
authors.initials: D
authors.lastname: Klein
authors.affiliation: Department of Neurology, Developmental Neurobiology, University of Würzburg, Wurzburg, Germany.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Martini
authors.affiliation: Department of Neuroscience and Pharmacology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Neurophysiology, Rigshospitalet, Copenhagen, Denmark. Electronic address: christian.krarup@regionh.dk.
authors.forename: Christian
authors.initials: C
authors.lastname: Krarup
mesh_terms: D000375:Aging / Q000235:genetics* / Q000473:pathology / Q000502:physiology*; D000818:Animals; D001369:Axons / Q000473:pathology / Q000502:physiology*; D004734:Energy Metabolism; D005260:Female; D015870:Gene Expression; D008810:Mice, Inbred C57BL; D009046:Motor Neurons / Q000473:pathology / Q000502:physiology*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D061566:Voltage-Gated Sodium Channels / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*
chemical_list: D020033:Protein Isoforms; D061566:Voltage-Gated Sodium Channels
keywords: Aging; Excitability; Internode; Nerve activity; Node of Ranvier; Voltage-gated sodium channels