Dedifferentiation of the Axolemma Associated with Demyelination

1981 ◽  
Vol 39 ◽  
pp. 496-497 ◽  
Author(s):  
J. Rosenbluth ◽  
A. Sumner ◽  
T. Saida
Keyword(s):  
Sodium Channels ◽  
Peripheral Nerves ◽  
Freeze Fracture ◽  
Fracture Analysis ◽  
Nerve Fibers ◽  
High Concentration ◽  
Myelinated Nerve ◽  
Spinal Roots ◽  
Myelin Deficient

Freeze-fracture analysis of myelinated nerve fibers has shown that the axolemma has a highly differentiated structure. The node is characterized by a high concentration of intramembranous particles, primarily in the E fracture face, which may represent the sodium channels known to be concentrated there, and the paranodal axolemma is characterized by a distinctive paracrystalline pattern that corresponds to the intercellular junction formed with the terminal “loops” of myelin lamellae. Studies of myelin formation in normal animals and of myelin-deficient mutant animals indicate that the development of these axolemmal specializations is profoundly influenced by the associated myelinforming cells. The present study considers whether or not nodal or paranodal specializations that have already formed persist after demyelination.In order to investigate this question, specimens of peripheral nerves were examined following exposure to an antiserum to galactocerebroside (GC), which is known to cause a predictable series of changes leading to demyelination. Freeze-fracture replicas of rat spinal roots exposed to anti-GC serum in situ for six hours showed marked changes in the paranodal axolemma.

scholarly journals Pharmacological Modifications of the Sodium Channels of Frog Nerve

1968 ◽  
Vol 51 (2) ◽  
pp. 199-219 ◽  
Author(s):  
Bertil Hille
Keyword(s):  
Sodium Channels ◽  
Nerve Fibers ◽  
Myelinated Nerve ◽  
Apparent Dissociation Constant ◽  
Specific Change ◽  
Myelinated Nerve Fibers ◽  
Sodium Activation ◽  
Sodium Inactivation ◽  
Na Ions ◽  
Ionic Forms

Voltage clamp measurements on myelinated nerve fibers show that tetrodotoxin, saxitoxin, and DDT specifically affect the sodium channels of the membrane. Tetrodotoxin and saxitoxin render the sodium channels impermeable to Na ions and to Li ions and probably prevent the opening of individual sodium channels when one toxin molecule binds to a channel. The apparent dissociation constant of the inhibitory complex is about 1 nM for the cationic forms of both toxins. The zwitter ionic forms are much less potent. On the other hand, DDT causes a fraction of the sodium channels that open during a depolarization to remain open for a longer time than is normal. The effect cannot be described as a specific change in sodium inactivation or as a specific change in sodium activation, for both processes continue to govern the opening of the sodium channels and neither process is able to close the channels. The effects of DDT are very similar to those of veratrine.

scholarly journals Time Course of Axon and Myelin Degeneration in Peripheral Nerves in Experimental Autoimmune Neuritis Rats

2019 ◽  
Vol 47 (4) ◽  
pp. 542-552 ◽  
Author(s):  
Emi Tomikawa ◽  
Mayu Mutsuga ◽  
Kojiro Hara ◽  
Chihiro Kaneko ◽  
Yuko Togashi ◽  
...  
Keyword(s):  
Peripheral Nerves ◽  
Time Course ◽  
Nerve Fibers ◽  
Neurological Symptoms ◽  
Experimental Autoimmune Neuritis ◽  
Histopathological Changes ◽  
Cell Cytoplasm ◽  
Myelinated Nerve ◽  
Transmission Electron ◽  
Experimental Autoimmune

Experimental autoimmune neuritis (EAN) is an animal model for Guillain–Barré syndrome (GBS), which results in neurological symptoms and histopathological changes in peripheral nerves. In this model, the correlation between the progression of the disease and the histopathological changes is not clear. To further examine histopathological changes in peripheral nerves in EAN rats, sciatic nerves were sampled at onset (day 10), peak (day 16), and recovery (days 22 and 25) of neurological symptoms in P2(57-81)-peptide-administered rats. Axon and myelin degeneration was observed by light microscopy at onset, degeneration became severe at peak, and persisted at recovery. Densities of myelinated nerve fibers and myelin areas decreased from day 10 to a minimum on day 22. Slight axon and myelin degeneration, such as accumulation of vesicles in axons and focal myelin splitting and folding, was observed by transmission electron microscopy at onset; severe degeneration, such as axonal loss, myelin ovoid, and demyelination, increased at peak; and regenerative changes, such as remyelination and enlargement of Schwann cell cytoplasm, occurred at recovery. These results suggest that EAN rats have histopathological similarities to some types of GBS patients and that EAN rats are a useful model to understand the pathogenesis of GBS.

scholarly journals Radicular Myelinopathy in Aging Rats

1981 ◽  
Vol 18 (3) ◽  
pp. 335-341 ◽  
Author(s):  
G. Krinke ◽  
J. Suter ◽  
R. Hess
Keyword(s):  
Spinal Cord ◽  
Peripheral Nerves ◽  
Nerve Fibers ◽  
Male Rats ◽  
Aging Rats ◽  
Myelin Sheaths ◽  
Naturally Occurring ◽  
Spinal Roots

Naturally occurring degenerative lesions of nerve fibers in the spinal cord, spinal roots and peripheral nerves in nine male rats 877 days old were swollen myelin sheaths, forming “myelin bubbles.” The myelin swellings were distributed throughout the spinal tracts and the peripheral nerves, but most frequently in the lumbar ventral spinal roots. Although most axons surrounded by swollen myelin were intact, some were constricted and degenerated, while others showed signs of remyelination.

scholarly journals Charges and Potentials at the Nerve Surface

1968 ◽  
Vol 51 (2) ◽  
pp. 221-236 ◽  
Author(s):  
Bertil Hille
Keyword(s):  
Potassium Channels ◽  
Sodium Channels ◽  
Voltage Dependence ◽  
Divalent Cations ◽  
Fold Increase ◽  
Nerve Fibers ◽  
Hydrogen Ions ◽  
Acidic Group ◽  
Myelinated Nerve ◽  
Bathing Medium

The voltage dependence of the voltage clamp responses of myelinated nerve fibers depends on the concentration of divalent cations and of hydrogen ions in the bathing medium. In general, increases of the [Ca], [Ni], or [H] increase the depolarization needed to elicit a given response of the nerve. An e-fold increase of the [Ca] produces the following shifts of the voltage dependence of the parameters in the Hodgkin-Huxley model: m∞, 8.7 mv; h∞, 6.5 mv; τn, 0.0 mv. The same increase of the [H], if done below pH 5.5, produces the following shifts: m∞, 13.5 mv; h∞, 13.5 mv; τn, 13.5 mv; and if done above pH 5.5: m∞, 1.3 mv; h∞, 1.3 mv; τn, 4.0 mv. The voltage shifts are proportional to the logarithm of the concentration of the divalent ions and of the hydrogen ion. The observed voltage shifts are interpreted as evidence for negative fixed charges near the sodium and potassium channels. The charged groups are assumed to comprise several types, of varying affinity for divalent and hydrogen ions. The charges near the sodium channels differ from those near the potassium channels. As the pH is lowered below pH 6, the maximum sodium conductance decreases quickly and reversibly in a manner that suggests that the protonation of an acidic group with a pKa of 5.2 blocks individual sodium channels.

scholarly journals The Permeability of the Sodium Channel to Metal Cations in Myelinated Nerve

1972 ◽  
Vol 59 (6) ◽  
pp. 637-658 ◽  
Author(s):  
Bertil Hille
Keyword(s):  
Sodium Channels ◽  
Ionic Composition ◽  
Reversal Potential ◽  
Metal Cations ◽  
Ionic Currents ◽  
Giant Axon ◽  
Nerve Fibers ◽  
Myelinated Nerve ◽  
Bathing Medium ◽  
Goldman Equation

The relative permeability of sodium channels to eight metal cations is studied in myelinated nerve fibers. Ionic currents under voltage-clamp conditions are measured in Na-free solutions containing the test ion. Measured reversal potentials and the Goldman equation are used to calculate the permeability sequence: Na+ ≈ Li+ > Tl+ > K+. The ratio PK/PNa is 1/12. The permeabilities to Rb+, Cs+, Ca++, and Mg++ are too small to measure. The permeability ratios agree with observations on the squid giant axon and show that the reversal potential ENa differs significantly from the Nernst potential for Na+ in normal axons. Opening and closing rates for sodium channels are relatively insensitive to the ionic composition of the bathing medium, implying that gating is a structural property of the channel rather than a result of the movement or accumulation of particular ions around the channel. A previously proposed pore model of the channel accommodates the permeant metal cations in a partly hydrated form. The observed sequence of permeabilities follows the order expected for binding to a high field strength anion in Eisenman's theory of ion exchange equilibria.

Microtubule and Neurofilament Densities in Amphibian Spinal Root Nerve Fibers: Relationship to Axoplasmic Transport

1973 ◽  
Vol 51 (11) ◽  
pp. 798-806 ◽  
Author(s):  
Richard S. Smith
Keyword(s):  
Dorsal Root ◽  
Dark Field ◽  
Nerve Fibers ◽  
Axoplasmic Transport ◽  
Spinal Root ◽  
Myelinated Nerve ◽  
Dorsal Roots ◽  
Dark Field Microscopy ◽  
Spinal Roots ◽  
Ventral Roots

Dark-field microscopy of living myelinated nerve fibers from the spinal roots of Xenopus laevis revealed many spherical organelles moving in the axoplasm of fibers from the ventral roots and in fibers just distal to the dorsal root ganglion. Similar organelles were present but few were seen to move along fibers from the dorsal roots central to the ganglion. This observation prompted an ultrastructural study of microtubule and neurofilament densities in the myelinated fibers of the spinal roots. The density of microtubules was significantly less in fibers from the central part of the dorsal roots than in the rest of the spinal root system. Neurofilament densities were equivalent in all parts of the roots. Microtubules showed a significant association with mitochondria in the ventral roots and in the dorsal roots distal to the ganglion, but no significant association was obtained for the dorsal roots central to the ganglion. The meaning of these results in the axoplasmic transport of large organelles is discussed.

scholarly journals The Inhibition of Sodium Currents in Myelinated Nerve by Quaternary Derivatives of Lidocaine

1973 ◽  
Vol 62 (1) ◽  
pp. 37-57 ◽  
Author(s):  
Gary R. Strichartz
Keyword(s):  
Sodium Channels ◽  
Voltage Dependence ◽  
Nerve Fibers ◽  
Sodium Currents ◽  
Myelinated Nerve ◽  
Variable Voltage ◽  
Electrical Gradient ◽  
A Site ◽  
Derivatives Of ◽  
Tonic Phase

The inhibition of sodium currents by quaternary derivatives of lidocaine was studied in single myelinated nerve fibers. Membrane currents were diminished little by external quaternary lidocaine (QX). QX present in the axoplasm (<0.5 mM) inhibited sodium currents by more than 90%. Inhibition occurred as the sum of a constant, tonic phase and a variable, voltage-sensitive phase. The voltage-sensitive inhibition was favored by the application of membrane potential patterns which produce large depolarizations when sodium channels are open. Voltage-sensitive inhibition could be reversed by small depolarizations which opened sodium channels. One explanation of this observation is that QX molecules enter open sodium channels from the axoplasmic side and bind within the channels. The voltage dependence of the inhibition by QX suggests that the drug binds at a site which is about halfway down the electrical gradient from inside to outside of the sodium channel.

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