[RNA synthesis in nuclei isolated from rabbit skeletal muscle following denervation and indirect electrostimulation].
Explore the source record for details and available documents.
Animals↗
SEARCH · Search PubMed
Results for “Muscle Denervation”
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Tomographic evaluation of size and X-ray density of normal and denervated human muscles.
Neuromuscular disease will lead to size changes, degeneration or destruction of muscle fibres. However, fat or connective tissue infiltration occurs and this prevents the use of simple measures to assess wasting. Computerized tomography will allow accurate assessment of this wasting. Five normal subjects and five patients with total traumatic denervation of radial or peroneal origin were examined. Denervated muscle was shown to have lower than normal cross-section and X-ray density. These reductions were not paralleled in circumference or limb volume. Recovery could be followed by tomography.
Absorptiometry, Photon↗
Lectin receptors in the cockroach neuromuscular system. II. Effects of denervation on muscle lectin receptors.
The binding of fluorescent derivatives of plant lectins to the 6 coxal depressor muscles in the leg of the cockroach was examined at 1, 2, 3 and 5 weeks after denervation. Histochemical analysis of the binding of the lectins to frozen sections of the muscles demonstrated that all detectable binding was to the surfaces of the muscle fibers. In addition, within one week of denervation those muscles which in the innervated state have different amounts of D-galactose and/or alpha-N-acetylgalactosamine on their surfaces, now all have identical amounts of these carbohydrates. Biochemical analysis of concanavalin A and wheat germ agglutinin glycoprotein receptors by sodium dodecylsulphate polyacrylamide gel electrophoresis indicated that approximately 17% of all the receptors detected altered their relative levels in denervated muscles. These changes were observed in those receptors that were present in equal amounts in each of the muscles as well as in those receptors that were distributed among the 6 muscles in a manner that correlated with innervation by an identified motor neuron. However, in spite of these changes that reduced the biochemical differences in the denervated CDMs it was still possible to distinguish among the 6 muscles by the nature of the Con A and WGA glycoprotein receptors. Denervated muscles still present biochemically different cell surfaces to regenerating motor neurons.
Animals↗
Sprouting and regression of neuromuscular synapses in partially denervated mammalian muscles.
1. The capacity of motor units to sprout after partial denervation and the ability of regenerating axons to suppress newly formed sprouts was examined in mouse skeletal muscle. Most experiments were performed on the peroneus tertius muscle which has 300 muscle fibres and eleven motor units ranging in strength from 1 to 35% of the total muscle tension. 2. Individual units, regardless of starting size, were able to sprout by up to 5 times their normal size following interruption of one of the two spinal roots innervating the muscle. In practive this resulted in muscles which had three or more units left intact becoming completely innervated again within 12 days. The majority of the sprouts probably innervated the old denervated end-plate sites. In the absence of re-innervation by the severed motor axons the sprouts persisted. In peroneus tertius about 60% of the sprouts giving rise to end-plates arose terminally and 40% collaterally. In soleus almost all the sprouts were terminal. 3. Re-innervation of the muscle by the severed motor axons occurred, starting from 14 days onwards after a crush injury, 19 days onwards after a cut. Re-innervation occurred even in muscles which presumably had no remaining denervated muscle fibres at the time regenerating axons reached the muscle. The re-innervating fibres grew to the original end-plate sites. 4. Following re-innervation the size of sprouted motor units apparently decreased. Thus, after re-innervation of muscles with three or more sprouted motor units, the sprouted units no longer caused contraction of all the muscle. However, the normal state of the muscle was not restored and the sprouted units continued to innervate more muscle fibres than normal, returning axons less than normal, and a small percentage of muscle fibres (ca. 10%) remained functionally innervated by axons of both sorts. 5. It is concluded that (i) in the mouse, axonal sprouting is a rapid and efficient process for restoring innervation; (ii) re-innervation of already innervated fibres can occur if the regenerating axons can return to existing end-plate sites; (iii) some of the redundant innervation is removed or repressed. 6. Possible mechanisms of competition between axon terminals are considered.
Animals↗
The external Ca(2+)-dependence of acetylcholine-induced contracture in single innervated and denervated skeletal muscle cells in mice.
We examined morphological differences and compared the Ca(2+)-dependence between acetylcholine (ACh)-contractures in normal and denervated skeletal muscle cells. ACh (1 microM - 1 mM) contracted the normal cells into a jackknife-shape. The higher the concentration of external Ca2+, the greater the ratio of responding cells/total cells observed and the sharper the angles of the "jackknives". ACh contracted the denervated cells into a compression-form, and the contraction was dependent on the external Ca2+. These results indicate that ACh-contractures in both normal and denervated cells are external Ca(2+)-dependent.
Acetylcholine↗
Alpha-aminoisobutyric acid uptake in vitro by the rat extensor digitorum longus muscle after denervation and tenotomy.
Explore the source record for details and available documents.
Aminoisobutyric Acids↗
Fibre-type specificity and effect of thyroid hormone on glucose 6-phosphate dehydrogenase activity in normal and denervated skeletal muscles of the rat.
Glucose-6-phosphate dehydrogenase activity increases following denervation of rat skeletal muscle. The specificity of this effect to muscle fibre type was studied. Basal activity of the dehydrogenase was higher in soleus, a muscle composed predominantly of type I fibres, than in extensor digitorum longus, a muscle composed predominantly of type IIa and b fibres. The enzymatic activity of the soleus was also greater than that of the red (RQ) and white (WQ) portions of quadriceps muscle (predominantly type IIa and type IIb fibres, respectively). Following denervation, glucose-6-phosphate dehydrogenase increased in extensor digitorum longus and RQ, but not in WQ or the soleus. Following chronic treatment of rats with 3,3',5-triiodothyronine, which converts type I muscle fibres to type II, the dehydrogenase activity increased in both denervated soleus and extensor digitorum longus. It is concluded that the effect of denervation on glucose-6-phosphate dehydrogenase activity is selective for type IIa (fast oxidative-glycolytic) muscle fibres.
Animals↗
In vivo expression patterns of MyoD, p21, and Rb proteins in myonuclei and satellite cells of denervated rat skeletal muscle.
MyoD, a myogenic regulatory factor, is rapidly expressed in adult skeletal muscles in response to denervation. However, the function(s) of MyoD expressed in denervated muscle has not been adequately elucidated. In vitro, it directly transactivates cyclin-dependent kinase inhibitor p21 (p21) and retinoblastoma protein (Rb), a downstream target of p21. These factors then act to regulate cell cycle withdrawal and antiapoptotic cell death. Using immunohistochemical approaches, we characterized cell types expressing MyoD, p21, and Rb and the relationship among these factors in the myonucleus of denervated muscles. In addition, we quantitatively examined the time course changes and expression patterns among distinct myofiber types of MyoD, p21, and Rb during denervation. Denervation induced MyoD expression in myonuclei and satellite cell nuclei, whereas p21 and Rb were found only in myonuclei. Furthermore, coexpression of MyoD, p21, and Rb was induced in the myonucleus, and quantitative analysis of these factors determined that there was no difference among the three myofiber types. These observations suggest that MyoD may function in myonuclei in response to denervation to protect against denervation-induced apoptosis via perhaps the activation of p21 and Rb, and function of MyoD expressed in satellite cell nuclei may be negatively regulated. The present study provides a molecular basis to further understand the function of MyoD expressed in the myonuclei and satellite cell nuclei of denervated skeletal muscle.
Age Factors↗
Insulin action in denervated skeletal muscle. Evidence that the reduced stimulation of glycogen synthesis does not involve decreased insulin binding.
The motor nerves to rat soleus and epitrochlearis muscles were sectioned 1-3 days before the muscles were incubated in vitro to assess insulin action and binding. The hormonal stimulation of [U-14C]glucose into glycogen in both muscles was decreased by over 80% after 3 days of denervation. Associated with the reductions in glycogen synthesis were losses in the ability of insulin to activate glycogen synthase. Even so, denervated and control muscles bound the same amounts of 125I-labeled insulin over a wide range of insulin concentrations. Scatchard analysis indicates that denervation changed neither receptor numbers nor affinities. The results presented strongly suggest that the loss of the ability of insulin to stimulate glycogen synthesis following denervation is the result of a postreceptor defect.
Animals↗
Mobility of extrajunctional acetylcholine receptors on denervated adult muscle fibers.
We report the lateral mobility of extrajunctional acetylcholine receptors (AChR), marked with fluorescently labeled alpha-bungarotoxin, on rat flexor digitorum brevis single muscle fibers maintained in cell culture. Mobility is measured by a modification of the fluorescence photobleaching recovery technique. The denervated rat flexor digitorum brevis muscle fibers exhibit a nonuniform distribution of AChR on their sarcolemmas. Diffusely distributed AChR have an average diffusion coefficient of about 2.5 X 10(-11) cm2/sec, somewhat lower than that of diffusely distributed AChR on embryonic rat myotubes in culture. Extrajunctional AChR aggregated into small clusters (less than 20 microns) have an average diffusion coefficient of about 5 X 10(-12) cm2/sec. Both the clustered and nonclustered extrajunctional AChR have lateral mobilities several orders of magnitude greater than that of junctional AChR.
Animals↗
Increased phosphorylation of nuclear protein in myonuclei isolated from denervated skeletal muscle.
The slow-twitch soleus muscle of the rat hindlimb was denervated by cutting the sciatic nerve in the midthigh on one side. A sham operation was performed on the contralateral side to provide a control soleus muscle. At 24, 48, 72, and 120 hours after these surgical procedures, the animals were sacrificed and the nuclei which were isolated from these muscles incubated in a phosphorylating medium containing [gamma-32P]ATP. At the 48 hour denervation period only, the in vitro phosphorylation of TCA-precipitable nuclear proteins was significantly increased compared to control values. Resolution of the SDS-solubilized nuclear proteins by polyacrylamide gel electrophoresis revealed that the increased phosphorylation was more marked in some phosphoproteins than others. The significance of these early denervation changes are discussed with respect to increases in the activities of the nuclear RNA polymerases and changes in the phosphorylation of cytosolic protein.
Animals↗
Reinnervation of long-term denervated rat muscle freely grafted into an innervated limb.
This experiment was designed to test the hypothesis that in the presence of regenerating nerve fibers long-term denervated skeletal muscle does not become reinnervated. This hypothesis was tested in rats by the transplantation of 22-month denervated extensor digitorum longus (EDL) muscles into the sites of EDL muscles in the contralateral, normally innervated legs. Two months after transplantation, the muscles contracted when stimulated via the motor nerve, and based on silver-acetylcholinesterase staining, all grafts possessed innervated motor end plates. Compared to values for control EDL muscles in old rats, the maximum force developed by standard free grafts in old rats was 19% and that of long-term denervated grafts was 7%. For standard free grafts, nerve stimulation produced a maximum force that was 81% of that produced by direct stimulation, and for control EDL muscles in young and old rats, the values were 96 and 90%, respectively. These results show that after long-term denervation rat muscles are capable of becoming functionally reinnervated, even though by the time of reinnervation the animals have attained an advanced age of 26 months.
Animals↗
Hyperpolarization of denervated skeletal muscle by lemakalim and its antagonism by glybenclamide and tolbutamide.
Innervated skeletal muscles are endowed with K+ channels activatable by K+ channel openers. It is of interest to know whether the denervation-induced depolarization is due to a deficiency of such a K+ channel. In denervated mouse diaphragm, lemakalim, a K+ channel opener, effectively hyperpolarizes membrane and reduces membrane resistance, spontaneous activity as well as twitch force reversibly. Reductions of transmembrane K+ gradient diminish the lemakalim-induced hyperpolarization. In voltage-clamped fiber, lemakalim induces a long-lasting outward current. A current clamp experiment suggests a reversal potential of around -90 mV. On innervated diaphragm, lemakalim hyperpolarizes membrane and increases conductance if the muscle is predepolarized by anodal current. Lemakalim, however, is much less effective in overcoming the depolarization caused by crotamine, which activates Na+ channel. The effects of lemakalim are not attenuated by blockades of membrane Na+, Ca++ and Cl- permeabilities. Glybenclamide and tolbutamide, blockers of ATP-regulated K+ channel, antagonize the effects of lemakalim at low concentrations and produce slight membrane hyperpolarizations in denervated muscle, but marked membrane depolarizations in innervated muscle at higher concentrations. Cs+ depolarizes both innervated and denervated diaphragms and reduces the hyperpolarizing effect of lemakalim. The results suggest that lemakalim hyperpolarizes denervated muscle via glybenclamide sensitive K+ channels. It is inferred that a reduction of membrane K+ conductance rather than an increase of Na+ or Ca++ conductance contributes to the denervation-induced depolarization.
Animals↗
Adenylate cyclase and guanylate cyclase of normal and denervated skeletal muscle.
Cyclic nucleotides mediate the intracellular effects of various extracellular influences. To explore the possibility that nerve-muscle influences are mediated by cyclic nucleotides, we studied the effect of denervation on the cyclase enzymes of rabbit gastrocnemius using the contralateral, unoperated limb as the control. Adenylate cyclase activity decreased dramatically after denervation, while guanylate cyclase activity increased several times in all tissue fractions studied. Neither enzyme demonstrated cholinergic responsiveness. The dramatic changes in cyclase activities following denervation could result from a role of these enzymes in the mediation of nerve-muscle influences.
Adenylyl Cyclases↗
Decline in titin content in rat skeletal muscle after denervation.
Titin, an elastic and giant myofibrillar protein, is responsible for generating passive tension and maintaining sarcomere structure in striated muscles. Several studies have reported attenuation of passive tension and disorganization of sarcomere in atrophic muscles, but the changes of titin have not been investigated after denervation. For this purpose, we used sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunofluorescent staining to examine titin in innervated and denervated tibialis anterior (TA) muscles of the rat. With increasing denervation time, we found a greater loss of titin than myosin heavy chain (MHC) and actin contents in atrophic TA muscle. The ratios of titin/MHC and titin/actin gradually decreased following denervation. In contrast, ratios of MHC/actin in the denervated groups showed no significant differences with the controls even at 56 days postdenervation. The ultrastructure of myofibrils also showed disturbed arrangements of myofilaments and a disorganized contractile apparatus in denervated muscle. Immunofluorescent staining displayed translocation of the titin epitope from the Z-line to the I-band, suggesting that the apparent cleavage of titin occurred near the Z-line region during the atrophying process. Our study provides evidence that titin is more sensitive to degradation than MHC and actin after denervation. Moreover, the titin decline results in the loss of titin-based sarcomeric integrity in atrophic muscle.
Actins↗
Tardy effect of neurogenic muscular atrophy by magnetic stimulation.
The influence of pulsed magnetic stimulation on denervated muscles was investigated in this study. Of 24 rats divided into three groups for experiment, 8 rats served as control; 16 rats with bilaterally severed sciatic nerves were divided into two groups for different modes of stimulation. Magnetic stimulation with a high power output that induced an intensive contraction of muscle was applied at one side-denervated gastrocnemius muscle for 1 mo in a group of rats; electric stimulation with high intensity at 6 Hz frequency and 1-ms pulse duration served as a contrast in the other group. Muscular weight, volume, fiber diameter and percentage of fiber types were measured after the experiment. A significant retardation of weight loss in denervated muscles via magnetic stimulation (P < 0.05) was confirmed by observed results. Type II fiber atrophy was retarded in denervated muscles by magnetic stimulation as well as in denervated muscles via electric stimulation. Magnetic stimulation, used as a method that induces muscular activity, was verified in this study as being capable of retarding denervated muscular atrophy. Its benefits of painless stimulation as well as deeply activated muscular contraction could be expected to function as a new model for rehabilitation of paralyzed muscles.
Animals↗
Molecular forms of the acetylcholine receptor from vertebrate muscles and Torpedo electric organ. Interactions with specific ligands.
Multiple forms of the acetylcholine receptor solubilised from cat denervated muscle were separated by velocity sedimentation centrifugation. The kinetic properties of the two main forms (with sedimentation coefficients of 9 S and 4 S) were investigated using a pure preparation of a suitable probe, [3H]propionyl-alpha-bungaro-toxin. The binding of this toxin to each of these forms of the muscle receptor was consistent with a simple bimolecular reaction with a homogeneous class of binding sites. Negligible dissociation of the receptor-toxin complex was observed. This behaviour was also found for the different forms of the acetylcholine receptor of chick embryo muscle and of Torpedo marmorata electric organ. Association rate constants for binding of the 3H-labelled alpha-toxin to receptor from chick embryo muscle and the 9-S and 4-S forms from cat denervated muscle were 0.54 X 10(5), 1.76 X 10(5) and 2.69 X 10(5) M--1 S--1 respectively, at 25 degrees C. The values obtained for the 9-S and 13-S forms of receptor from T. marmorata were 4.51 X 10(5) and 9.93 X 10(5) M--1 S--1 respectively. The reaction of the 3H-labelled alpha-toxin with the receptor was second-order and linear in the presence of an antagonist, as in its absence, for the 4-S and 9-S forms of the cat denervated muscle receptor. This reaction of the receptor was inhibited by cholinergic ligands, with Ki values for two antagonists tested being greater with the 4-S form than with the 9-S form. Apparent negative interaction is observed for antagonists with this receptor, with Hill coefficients of about 0.78 and 0.64 for the 4-S and 9-S forms respectively. A ligand-induced affinity increase, produced by the agonists but not by the antagonists, was observed in this reaction for both forms of the muscle receptor. Two agonists tested showed no difference between these forms in their high-affinity states in either their binding affinities or Hill coefficients.
Animals↗
Insulin action in denervated rat hemidiaphragms. Decreased hormonal stimulation of glycogen synthesis involves both glycogen synthase and glucose transport.
Rat hemidiaphragms were denervated in vivo and then incubated in vitro to assess the ability of insulin to stimulate glycogen synthesis. Denervation for 1 day resulted in 50% decreases in the stimulation by insulin of [U-14C]glucose incorporation into glycogen, and in both the basal and the insulin-stimulated activity ratios (activity minus glucose-6-P/activity plus glucose-6-P) of glycogen synthase; however, the stimulation of 2-deoxyglucose uptake by insulin was not affected by 1 day of denervation. The hormonal stimulation of [U-14C]glucose into glycogen was decreased by 90% after 3 days of denervation. At this time, the stimulation of 2-deoxyglucose uptake by insulin was also reduced and the synthase activity ratios remained depressed. Consistent with its reduced effect on glucose transport, the hormone did not increase glucose-6-P in the 3-day denervated muscles. Furthermore, the Ka for activation of glycogen synthase by glucose-6-P was higher in denervated muscles, and denervation abolished the effect of insulin on decreasing the Ka. The results presented demonstrate that denervation rapidly reduces the extent to which glycogen synthase can be activated by insulin, and has a later effect on decreasing the stimulation of glucose transport. These two effects act synergistically to markedly decrease the hormonal stimulation of glycogen synthesis.
Animals↗