title: Matching mitochondria to metabolic needs at nodes of Ranvier.
abstract: Myelinated axons conduct nerve impulses at high speed using a unique mode of excitation, referred to as saltatory conduction, which is enabled structurally by the narrowing of the site of action potentials to a tiny gap in the axon called the node of Ranvier. With this structural specialization comes an interesting metabolic matching problem. How do mitochondria find and supply energy to these tiny nodes of Ranvier distributed sparsely along a myelinated axon? Does the intense Na(+) influx at the node, which is produced by the highest known sodium channel density in all excitable membranes, help guide where mitochondria stop? Evidence suggests that during excitation in the peripheral nervous system, Na(+) influx recruits mitochondria to the node by triggering Ca(2+) elevation and activating Na(+) pumps. Intriguingly, indirect evidence suggests that in the central nervous system, activity recruits mitochondria to the internode (myelin-covered portion of the axon). Metabolic dysfunction thus might produce spatially distinct lesions in PNS and CNS myelinated fibers. Future dissection of regional variation in mitochondrial biology in myelinated axons using live imaging will likely yield surprises about sites of vulnerability in demyelinating diseases and clues for therapeutic intervention strategy.
authors.affiliation: Department of Physiology, University of Wisconsin School of Medicine, Madison, WI 53706, USA. chiu@physiology.wisc.edu
authors.forename: Shing Y
authors.initials: SY
authors.lastname: Chiu
mesh_terms: D000818:Animals; D003711:Demyelinating Diseases / Q000378:metabolism / Q000473:pathology; D004734:Energy Metabolism / Q000502:physiology*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism* / Q000502:physiology; D009413:Nerve Fibers, Myelinated / Q000378:metabolism*; D009431:Neural Conduction / Q000502:physiology*; D011901:Ranvier's Nodes / Q000378:metabolism* / Q000502:physiology