title: Formation and disruption of functional domains in myelinated CNS axons.
abstract: Communication in the central nervous system (CNS) occurs through initiation and propagation of action potentials at excitable domains along axons. Action potentials generated at the axon initial segment (AIS) are regenerated at nodes of Ranvier through the process of saltatory conduction. Proper formation and maintenance of the molecular structure at the AIS and nodes are required for sustaining conduction fidelity. In myelinated CNS axons, paranodal junctions between the axolemma and myelinating oligodendrocytes delineate nodes of Ranvier and regulate the distribution and localization of specialized functional elements, such as voltage-gated sodium channels and mitochondria. Disruption of excitable domains and altered distribution of functional elements in CNS axons is associated with demyelinating diseases such as multiple sclerosis, and is likely a mechanism common to other neurological disorders. This review will provide a brief overview of the molecular structure of the AIS and nodes of Ranvier, as well as the distribution of mitochondria in myelinated axons. In addition, this review highlights important structural and functional changes within myelinated CNS axons that are associated with neurological dysfunction.
authors.affiliation: Department of Neuroscience, Cell Biology, and Physiology, Boonshoft School of Medicine, Wright State University, Dayton, OH, United States.
authors.forename: Ryan B
authors.initials: RB
authors.lastname: Griggs
authors.affiliation: Department of Neuroscience, Cell Biology, and Physiology, Boonshoft School of Medicine, Wright State University, Dayton, OH, United States.
authors.forename: Leonid M
authors.initials: LM
authors.lastname: Yermakov
authors.affiliation: Department of Neuroscience, Cell Biology, and Physiology, Boonshoft School of Medicine, Wright State University, Dayton, OH, United States. Electronic address: keiichiro.susuki@wright.edu.
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Susuki
mesh_terms: D000200:Action Potentials; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001369:Axons / Q000502:physiology*; D001930:Brain Injuries / Q000378:metabolism / Q000473:pathology; D002154:Calpain / Q000378:metabolism; D002490:Central Nervous System / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D009103:Multiple Sclerosis / Q000378:metabolism / Q000473:pathology; D009186:Myelin Sheath / Q000502:physiology*; D011901:Ranvier's Nodes / Q000502:physiology
chemical_list: D002154:Calpain
keywords: Axon initial segment; Calpain; Mitochondria; Neurological disease; Node of Ranvier