Ionic channels and signal conduction in single remyelinating frog nerve fibres. 1988

P Shrager
Department of Physiology, University of Rochester Medical Center, NY 14642.

1. Ionic currents have been measured in single demyelinated and remyelinating frog sciatic nerve fibres by means of the loose patch clamp technique. Axons were demyelinated by a surgical intraneural injection of lysolecithin and recovery was followed for up to 5 months. 2. Removal of myelin debris continued for the first 2 weeks post-injection. Proliferating Schwann cells were then seen within the lesion. As remyelination proceeded new nodes of Ranvier were formed in regions that previously were internodal. Original nodes, marking the transition from old to new myelin, could be identified at all stages. 3. Peak amplitudes of internodal transient inward Na+ currents were constant over the first 2 months and increased by about 60% after 5 months. Internodal currents in remyelinated axons were recorded after a second injection of lysolecithin to remove the thin myelin sheath. 4. Records from paranodal sites neighbouring transition nodes contained transient outward currents that were strongly voltage dependent and seemed to reflect activation of a very high density of Na+ channels just outside the patch. This sharp gradient in channel density at original nodes persisted throughout the period of remyelination studied suggesting that lateral diffusion from these sites is limited. These currents were never seen at internodal sites nor were they found at new nodes of Ranvier. 5. Paranodal inward current amplitudes in new nodes were similar to those in original (transition) nodes. 6. No transient inward Na+ currents were detected in Schwann cells adhering to demyelinated axons or free standing within the area of the lesion. 7. Conduction in single remyelinating fibres was studied by measuring membrane currents that flowed in response to an invading propagating action potential. At 2 weeks post-injection, prior to the formation of myelin, conduction was decremental, but activation of internodal Na+ channels allowed signals to penetrate further into the demyelinated zone than would have been possible by passive spread alone. After an additional 3 weeks, following formation of thin myelin sheaths, conduction was significantly improved and the fractional activation of Na+ channels was increased. 8. The results suggest that Na+ channels at new nodes of Ranvier come neither from original nodes nor from Schwann cells. They may represent a moderate aggregation of existing internodal channels. New nodes seem to possess a gradient of Na+ channel density that is much less steep than that at original nodes. Continuous conduction appears to be limited to short (approximately 0.2 mm) lengths of demyelinated axons.(ABSTRACT TRUNCATED AT 400 WORDS)

UI MeSH Term Description Entries
D007473 Ion Channels Gated, ion-selective glycoproteins that traverse membranes. The stimulus for ION CHANNEL GATING can be due to a variety of stimuli such as LIGANDS, a TRANSMEMBRANE POTENTIAL DIFFERENCE, mechanical deformation or through INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS. Membrane Channels,Ion Channel,Ionic Channel,Ionic Channels,Membrane Channel,Channel, Ion,Channel, Ionic,Channel, Membrane,Channels, Ion,Channels, Ionic,Channels, Membrane
D008854 Microscopy, Electron Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen. Electron Microscopy
D009186 Myelin Sheath The lipid-rich sheath surrounding AXONS in both the CENTRAL NERVOUS SYSTEMS and PERIPHERAL NERVOUS SYSTEM. The myelin sheath is an electrical insulator and allows faster and more energetically efficient conduction of impulses. The sheath is formed by the cell membranes of glial cells (SCHWANN CELLS in the peripheral and OLIGODENDROGLIA in the central nervous system). Deterioration of the sheath in DEMYELINATING DISEASES is a serious clinical problem. Myelin,Myelin Sheaths,Sheath, Myelin,Sheaths, Myelin
D009413 Nerve Fibers, Myelinated A class of nerve fibers as defined by their structure, specifically the nerve sheath arrangement. The AXONS of the myelinated nerve fibers are completely encased in a MYELIN SHEATH. They are fibers of relatively large and varied diameters. Their NEURAL CONDUCTION rates are faster than those of the unmyelinated nerve fibers (NERVE FIBERS, UNMYELINATED). Myelinated nerve fibers are present in somatic and autonomic nerves. A Fibers,B Fibers,Fiber, Myelinated Nerve,Fibers, Myelinated Nerve,Myelinated Nerve Fiber,Myelinated Nerve Fibers,Nerve Fiber, Myelinated
D009431 Neural Conduction The propagation of the NERVE IMPULSE along the nerve away from the site of an excitation stimulus. Nerve Conduction,Conduction, Nerve,Conduction, Neural,Conductions, Nerve,Conductions, Neural,Nerve Conductions,Neural Conductions
D011901 Ranvier's Nodes Regularly spaced gaps in the myelin sheaths of peripheral axons. Ranvier's nodes allow saltatory conduction, that is, jumping of impulses from node to node, which is faster and more energetically favorable than continuous conduction. Nodes of Ranvier,Nodes, Ranvier's,Ranvier Nodes,Ranviers Nodes
D000200 Action Potentials Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli. Spike Potentials,Nerve Impulses,Action Potential,Impulse, Nerve,Impulses, Nerve,Nerve Impulse,Potential, Action,Potential, Spike,Potentials, Action,Potentials, Spike,Spike Potential
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012583 Schwann Cells Neuroglial cells of the peripheral nervous system which form the insulating myelin sheaths of peripheral axons. Schwann Cell,Cell, Schwann,Cells, Schwann
D012584 Sciatic Nerve A nerve which originates in the lumbar and sacral spinal cord (L4 to S3) and supplies motor and sensory innervation to the lower extremity. The sciatic nerve, which is the main continuation of the sacral plexus, is the largest nerve in the body. It has two major branches, the TIBIAL NERVE and the PERONEAL NERVE. Nerve, Sciatic,Nerves, Sciatic,Sciatic Nerves

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