The action of local anesthetics on myelin structure and nerve conduction in toad sciatic nerve

X-ray scattering and electrophysiological experiments were performed on toad sciatic nerves in the presence of local anesthetics. In vitro experiments were performed on dissected nerves superfused with Ringer's solutions containing procaine, lidocaine, tetracaine, or dibucaine. In vivo experiments were performed on nerves dissected from animals anesthesized by targeted injections of tetracaine-containing solutions. In all cases the anesthetics were found to have the same effects on the x-ray scattering spectra: the intensity ratio of the even-order to the odd-order reflections increases and the lattice parameter increases. These changes are reversible upon removal of the anesthetic. The magnitude of the structural changes varies with the duration of the superfusion and with the nature and concentration of the anesthetic molecule. A striking quantitative correlation was observed between the structural effects and the potency of the anesthetic. Electron density profiles, which hardly showed any structural alteration of the unit membrane, clearly indicated that the anesthetics have the effect of moving the pairs of membranes apart by increasing the thickness of the cytoplasmic space. Electrophysiological measurements performed on the very samples used in the x-ray scattering experiments showed that the amplitude of the compound action potential is affected earlier than the structure of myelin (as revealed by the x-ray scattering experiments), whereas conduction velocity closely follows the structural alterations.     

Changes in fatty acid composition of peripheral nerve myelin in essential fatty acid deficiency

Severe essential fatty acid deficiency (EFAD) was induced by feeding weanling rats a diet free of essential fatty acids 8 months after weaning. The fatty acid compositions of phospholipids and glycosphingolipids in peripheral nerve myelin were compared in rats with and without EFAD. With the deficient diet, 20:3ω9 was found in the major myelin phospholipids. The level of 18:1 was increased and the levels of 18:2ω6, 20:4ω6, and 22:4ω6 were decreased. Both sphingomyelin and cerebroside showed higher proportion of 24:1 and lower proportions of 24:0 in EFA-deficient rats than in control rats. The fatty acid chain elongating system in myelin cerebroside was also depressed by EFAD. A two- to sevenfold increase of the ratio 20:4ω6 to 20:3ω6 was found in myelin phospholipids of regenerated nerve from rats fed control diet. However, this ratio was suppressed by EFAD diet. The biochemical index (20:3ω9/20:4ω6) for EFAD was not affected by crush injury. These results suggest that dietary EFAD in postweaning rats can induce fatty acid alterations in peripheral nerve myelin without resulting in detectable changes in function or structure and that myelin lipids may be sequestered and reused during nerve degeneration and regeneration.     

The effects of hydrostatic pressure upon the normal and narcotized nerve fiber

The properties of the giant axon of the squid Loligo pealii were studied at different hydrostatic pressures from 14.7 to 16,000 psi. At 4000 psi the resting potential, the membrane resistance, membrane capacity, the conduction velocity, the amplitude of the action potential, and the maximal change in the membrane impedance during activity were only slightly affected. At the same pressure the duration of the falling phase of the action potential was increased by about 40 to 60 per cent and the duration of the rising phase by about 20 to 35 per cent. The duration of the membrane impedance change during activity was increased by 50 to 100 per cent at 4000 psi. At pressures even slightly above atmospheric the threshold membrane current was appreciably reduced. At about 3000 to 7000 psi the fiber fired spontaneously. At pressures considerably above 5000 psi the membrane resistance decreased to about one-half to one-third the original value. The narcotizing effect upon the nerve fiber of 3 to 7 per cent ethanol was partly or almost completely opposed by low temperatures or high pressures.     

Changes in the fatty-acid profile of cyanide-utilizing Yersinia species

A cyanide-utilizing Yersinia species was isolated from the cyanide-bearing gold-plating industrial wastewater. Analysis of the fatty acid composition of the organism revealed that it contains large amounts of saturated fatty acids. The unsaturated hydroxy- and cyclopropyl-ring-bearing fatty acids are present in low concentrations. A comparison of the fatty acid composition with other Yersinia species shows that the genus Yersinia appears homogeneous, and that fatty-acid data of Yersiniae do not reflect the distance between Yersiniae species.     

Supramolecular aggregation and organization in peripheral nerve myelin

Under certain preparative conditions the lipid bilayers of glutaraldehyde-fixed, PNS myelin demonstrate a marked compartmentalization, which can be augmented by lipid extraction following sectioning. The results are interpreted as indicating a supramolecular domain pattern of arrangement centered upon the transmembrane protein (P0) molecules. The latter are thought to be surrounded by annuli of substantially immobilized phospholipids. In the lamellar planes particular lipids are considered to have a nonrandom distribution. The visualization of bilayer compartmentalization was seen only in negatively stained sections obtained from unembedded or glutaraldehyde-urea-embedded myelin. Lipids were unextracted in the basic preparations except in so far as some unfixed, amphipathic molecules escaped at the trough-fluid interface at the time of sectioning, an observed phenomenon which probably aided in the visualization of the compartmentalization. Visualization was also augmented by surface tension expanding section fragments as they floated on the trough fluid. All stages of transition between well-ordered myelin and dispersed globular units were commonly to be found. Deliberately delipidated myelin exposed more sharply defined and smaller globular units in bilayer regions, but even these are regarded as being supramolecular aggregates including residual lipid annuli around the transmembrane proteins. The addition of cadmium ions as a "fixative" for lecithin seemed to improve the preservation of glutaraldehyde-urea-embedded myelin but was not strictly necessary to reveal its domain structure. A secondary tannic acid fixation was required to process unembedded myelin so as to reveal the fundamental compartmentalization of its lipid bilayers.     

Influence of nerve fiber K+ depolarization and altered membrane protein conformation on the state of myelin

Using Raman spectrometry and fluorescence microscopy, we studied the rearrangement of carotenoid molecules and membrane-bound Ca _mb ²⁺ in myelinated nerve fibers after K⁺ depolarization, K⁺-channel blocking, and altering the membrane protein conformation. We observed a decrease in Ca _mb ²⁺ and an increase of microviscosity in myelin after depolarization. Changes in Ca _mb ²⁺ and microviscosity were registered after blocking the K⁺ channels and modifying proteins with PCMB. Our results suggest an interconnection between the condition of nerve fiber membrane proteins, Ca _mb ²⁺ distribution, and myelin microviscosity.     

Effects of solvents on the structure of myelin in the sciatic nerve of the frog

• 1.1. The effects of ethyl alcohol, ether, and acetone on the X-ray diffraction patterns of fresh nerve and dried nerve have been studied.
• 2.2. Ethyl alcohol and acetone vapours produced rapid changes in the diffraction pattern of fresh nerve. Ether vapour had relatively little effect.The effects of mixtures containing varying proportions of alcohol or acetone in Ringer solution were similar to those of the solvent vapours.Ethyl alcohol, acetone, and ether, all readily affected the spacings below 70 A in the dried nerve pattern. The spacings above 70 Å were much more susceptible to alcohol treatment than to ether and acetone.
• 3.3. The results are in keeping with the existence in myelin of a highly-ordered lipid-lipoprotein unit.
     

Fluorescence anisotropy and myelin structure. II. Azimuth characteristic of surviving nerve fibers]

The dependence of fluorescence polarization of stained nerve fibres on the angle between the fibre axis and electrical vector of exciting light (azimuth characteristics) has been considered. Evidence is provided that the azimuth characteristics of stained nerve fibres depends on dye molecules adsorbed on the myelin sheath membranes. From the previous calculations it may be concluded that part of the dye molecules are oriented at a small angle to the geometrical axis of the nerve fibre.     

Effect of magnetic field on excitation propagation in a nerve fiber innervating a blood vessel]

It was shown that external magnetic field indirectly affects the blood flow due to the increments of local currents in the surroundings of action potentials that propagate along nerve fibres innervating the smooth muscle cells of the vessel wall. This reduces their tension due to nonconcurrent propagation of excitation in space and to changes in the frequency of action potentials. The dependence of this effect on the electrophysiological parameters is estimated.