[Responses of the muscle spindles of denervated muscles to mechanical stimulation].
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ACh contractures of denervated lumbricalis muscles of rats were washed in Tris-methanesulfonate solutions and in sucrose solutions. The peak tension was diminished by about 80% following a 30 min exposure to solutions containing 400-600 mM glycerol when Tris solutions were used in the testing period, and by about 50% when sucrose solutions were used. The amplitude of the membrane potential changes provoked by ACh was decreased by about 36% following the glycerol treatment. The treatment had no effect on the ACh-induced 45Ca uptake of muscles. Electron microscopy of the glycerol-treated muscles showed widespread vacuolization apparently originating from swelling and disruption of the T system. It was concluded that ACh receptors which arise in the muscle membrane following nerve section are distributed in the external surface membrane and in the membranes of the T system.
A systematic study of dystrophy-denervation in human muscle showed minimal morphometabolic differences between dystrophic and dystrophic-denervated muscle. The only certain conclusion is that denervation influences the rhythm of evolution of the dystrophy without impressing any of the few characteristics considered at present as peculiar to denervation.
Intact soleus and extensor digitorum longus muscles in the rat were freely grafted to the contralateral leg after either no preliminary treatment or 14 days prior denervation. Normal muscle grafts during the first week were characterized by a central zone of degenerating original muscle fibers (disappearing by 7-9 days) and a peripheral zone, containing regenerating muscle as well as small numbers of surviving original muscle fibers. A radial gradient of regeneration was establihed, with more mature muscle at the periphery and less mature muscle toward the center. Denervated grafts were characterized by rapid degeneration (within 2-3 days) of original muscle fibers in the central area, rapid appearance of regenerating muscle fibers (e.g. cross striations by 5 days) with uniform levels of differentiation throughout the graft and larger numbers of surviving original muscle fibers at the periphery. During the first week, stages of muscle differentiation in denervated grafts were attained 1-2 days earlier than comparable stages in normal grafts. Later stages of muscle differentiation were similar in both types of grafts. Histochemical studies revealed a loss of enzyme activity (phosphorylase, ATPase and SDH) in the center of early (2-4-day) normal and denervated grafts. Denervated grafts, however, possessed a thicker peripheral rim of enzymatically active surviving muscle fibers than normal grafts. In both types of grafts the old muscle fibers in the center were replaced by enzymatically active regenerating muscle fibers which stained uniformaly (ATPase) until 30 days. By 60 days a mixed fiber pattern had developed. Muscle spindles were found within the grafts.
Ca2+ATPase activity and light chains of myosin, fractionated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, in developing, adult and denervated fast, slow and cardiac muscles of the rat, guinea-pig, cat, rabbit and chick were studied. It has been shown that in normal adult muscles the electrophoretic pattern of light chains of myosin reflects the myosin ATPase activity only when muscles from the same animal species are compared. In homologous muscles from adult animals differing in size, the size-dependent difference in myosin ATPase activity is not revealed in the electrophoretic pattern. Both in developing and in denervated muscle, changes in myosin ATPase activity are either connected with changes in the pattern of light chains of myosin or this pattern does not change. This relation is different in fast and slow muscles and also differs in chick and rabbit muscles. There are several possibilities of explaining the relation between ATPase activity of myosin and the pattern of light chains of myosin. The observation that myosin from the soleus muscle of 1-month-old rabbit contains light chains corresponding to both fast and slow type of myosin, indicates that the change in myosin ATPase activity during development is due to changes in the ratio between the fast and slow type of myosin.
After preliminary conditioning depolarizations, single muscle fibers of the frog were tested for ability to contract in response to depolarization by 100 mM K+ Ringer solution. Denervated fibers (6-42 days) lose their ability to produce a 100 mM K+ contracture more rapidly than do control fibers. This decrease in 100 mM K+ contracture size (inactivation) is dependent on length of exposure to and magnitude of the conditioning depolarization and on the calcium concentration in the external medium. At 0.4 mM Ca++, the inactivation is 3 times faster than at 1.5 mM Ca++. The rate of contracture loss is not correlated with fiber diameter or the number of days after failure of neuromuscular transmission, and the preliminary conditioning depolarizations do not affect the rate of terminal relaxation from the 100 mM K+ contractures.
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1. Motoneurones provide trophic control of some of the functional characteristics of skeletal muscle fibres. This study has been designed to test whether the adenylate cyclase: cyclic AMP system may offer one potential mechanism for the mediation of neurotrophic regulation. 2. The concentration of cyclic AMP was measured at various intervals after muscle denervation. Muscle cyclic AMP concentration increases for the first 2 days after nerve section. It reaches a maximum value at 48 h and subsequently returns to the control value at 7 days. 3. Cyclic AMP concentration is unchanged by muscle disuse for the first 3 days following limb immobilization. Four days after immobilization, however, cyclic AMP increases in both the disused and contralateral control muscles. This phenomenon has been tentatively ascribed to some aspect of the inflammatory response. 4. Changing the level of nerve section, and therefore the length of the residual nerve stump, changes the temporal pattern of the increase in muscle cyclic AMP concentration. 5. Reinnervation of a denervated muscle produces a decrease in muscle cyclic AMP concentration. 6. It is concluded from the results that some aspect of nerve function provides trophic regulation of the muscle adenylate cyclase: cyclic AMP system. The mechanisms by which this regulation may be applied are considered in the Discussion.
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In cat skeletal muscles, the major part of specific [3H]-ouabain binding was found in the sympathetic nerve endings of red, slow muscle fibres. Skeletal muscle denervation increased specific [3H]-ouabain binding to muscle membrane preparation. This increase may be involved in the development of spontaneous fibrillation in the denervated muscle.
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Abnormalities have been noticed in the phospholipid and cholesterol composition of the atrophied gastrocnemius muscle of frog denervated for 1 month. Cholesterol : phospholipid molar ratios in the muscle increased on denervation. Sphingomyelin and cardiolipin fractions increased in contrast to phosphatidyl choline, phosphatidyl serine and phosphatidyl ethanolamine in the sarcoplasmic reticulum (SR) of denervated muscle. Na-azide sensitive Ca2+ ATPase activity of the mitochondria did not alter whereas that of SR decreased on denervation. Phospholipase C digestion impaired the organelle Ca2+-ATPase activity. The above abnormalities in enzyme activities have been correlated to the changes in the lipid composition of the denervated muscle. On the basis of these changes it is discussed that the primary change in the muscle due to denervation is the change in the permeability of the membrane.
The properties of sarcomplasmic reticulum Ca-pump from normal and denervated rabbit muscles were investigated. Ca+2 ion transport in denervated muscle reticulum was subject to Michaelis-Menten kinetics. The rate of fast Ca2+ outflux from the vesicles was enhanced after denervation; this caused a decrease in the transport efficiency and an increase of the "basic" ATP-ase. At the same time the rate of Ca2+ accumulation and the Ca-ATP-ase transport activity were enhances by a factor of 1.5. Kinetic properties of the denervated sarcoplasmic reticulum proved to be closely related to the features of the excitation-contraction cycle in these muscles.