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.     

Recovery of rat skeletal muscles after partial denervation is enhanced by treatment with nifedipine

Following partial denervation of adult rat skeletal muscle intact axons sprout to reinnervate denervated muscle fibres and increase their territory. The extent of this increase is limited and may depend on the ability of axon terminals to form and maintain synaptic contacts with the denervated muscle fibres. Here we tested the possibility whether reducing Ca²⁺ entry into presynaptic nerve terminals through dihydropyridine sensitive channels may allow more nerve–muscle contacts to be formed and maintained. Hindlimb muscles of adult Wistar rats were partially denervated by removing a small segment of the L4 or L5 spinal nerve on one side. A nifedipine-containing silastic rubber strip was subsequently implanted close to the partially denervated soleus or extensor digitorum longus (EDL) muscles in some animals. In control experiments silastic strips which did not contain nifedipine were used. Several weeks later isometric contractions were recorded, to determine the effect of (a) partial denervation and (b) nifedipine treatment on force output and motor unit numbers. The tension produced by nifedipine treated partially denervated muscles was 82% and 79% of the unoperated contralateral value for soleus and EDL, respectively. This was significantly greater than in untreated muscles, which only produced 61% and 48%, respectively. Mean motor unit force was also significantly larger with nifedipine treatment. Histological analysis revealed that a significantly larger proportion of the total number of muscle fibres remained in nifedipine-treated partially denervated muscles (soleus, 90% and EDL, 101%) compared with untreated muscles (soleus, 51% and EDL, 66%). Thus the number of neuromuscular contacts was increased with nifedipine treatment.     

Restoration of denervated skeletal muscle transplants after reinnervation in rats

The present study describes reinnervation and restoration of rat skeletal muscle denervated for the duration of 3, 6 or 12 months. Denervation of extensor digitorum longus (EDL) muscle was achieved by cutting and ligating the donor rat sciatic nerve in situ. At 3, 6 and 12 months, the denervated EDL muscles were removed and transplanted into an innervated normal leg of another rat. In addition, normal (i.e., no prior denervation) muscles were transplanted as controls for comparison. The muscles were analyzed at 4 and 12 weeks after transplantation. The EDL muscle weight and myofiber size decreased with extended denervation times. After transplantation, the muscles underwent regeneration and reinnervation, and recovered as determined by an increase in muscle mass and myofiber size. The 3-month denervated muscle regenerates recovered completely, and were similar to the non-denervated normal muscle regenerates. Reinnervation, and partial recovery of muscle weight and myofiber size was observed in 6- and 12-month denervated muscle transplants. These results document that while regeneration and reinnervation does occur in denervated muscles after transplantation, the extent of recovery is related to the duration of denervation.     

Studies on the regenerative recovery of long-term denervated muscle in rats

Denervated extensor digitorum longus (EDL) muscles in rats rapidly lose mass and contractile force. After two months of denervation, mass and maximum tetanic force have fallen to 31% and 2% of the values of contralateral control muscles. Our purpose was to determine if grafting a long-term denervated muscle into an innervated site provides an effective means of restoring its structure and function. EDL muscles that had been denervated for periods of 2-12 months were freely grafted into innervated sites of EDL muscles in 4-month inbred host animals. Contralateral normally innervated EDL muscles from the same donors were implanted into the opposite legs of the same hosts. Two months after grafting, the muscles were removed and measurements were made in vitro of isometric contractile properties. The grafts were then prepared for morphological analysts. In all cases, the maximum forces generated by innervated grafts of denervated muscles were greater than those generated by denervated muscles. However, when compared with grafts of control muscles in the contralateral limb, grafts of previously denervated muscles showed a steady decline in structural and functional recovery corresponding to the time of previous denervation. The decline was especially pronounced for muscles denervated between 2 and 7 months prior to grafting. Grafts of 7-month denervated muscles were restored to only 17% of the maximum tetanic force of contralateral control grafts compared with 83% for grafts of 2-month denervated muscles. The longer a muscle had been denervated prior to grafting, the higher proportion of thin atrophic muscle fibers it contained. We conclude that grafting into an innervated site improves the mass and maximum force of a muscle over the denervated state, but the longer the period of prior denervation the poorer the recovery of the grafted muscles.     

Number of contractions to maintain mass and force of a denervated rat muscle

Within 5 weeks, denervated extensor digitorum longus (EDL) muscles of rats lose 66% of mass, 91% of force, and 76% of fiber cross-sectional area (CSA). We previously determined the parameters of electrical stimulation for denervated rat EDL muscles to generate tetanic contractions sufficient to maintain mass and force close to control values. Using these parameters, we tested the hypothesis that a range exists for number of contractions per day, below and above which values for mass, maximum force, and fiber CSA are lower than values for innervated control muscles. For 5 weeks, denervated EDL muscles were stimulated to generate between 25 and 5000 contractions daily with contractions separated by constant intervals of rest, repeated 24 h per day. Force was not maintained with fewer than 200 or more than 800 contractions daily, whereas mass and fiber CSA were not maintained with fewer than 50 contractions daily. Protocols of stimulation that maintain muscle mass and force during prolonged periods of denervation may minimize problems clinically associated with denervation atrophy.     

Factors affecting denervation-like changes at the neuromuscular junction during aging

The ability to sustain synaptic transmission diminishes with aging. To determine whether this is accompanied by alterations in the structure of the synapse, end-plate architecture was examined in EDL muscles from 10- to 25-month rats. There was a significant age-related increase in end-plate area and a decrease in the number of nerve terminals per end plate. Furthermore, the percentage of end plates with ultraterminal sprouts increased dramatically with age. To compare the morphological changes associated with aging to the changes in response to denervation, EDL muscles from 10- and 25-month animals were partially denervated. Both end-plate area and ultraterminal sprouting increased, while terminal number decreased following denervation in the 10-month muscles. To determine whether the age- and denervation-associated changes were accompanied by alterations in muscle-derived nerve-outgrowth factors, in vitro assays were performed. Neurite outgrowth was quantified from embryonic motoneurons incubated with muscle extract, or grown on cryostat-cut muscle cross sections from 10- and 25-month innervated and denervated EDL muscles. Both aged and denervated muscles induced greater degrees of neurite outgrowth compared with younger innervated muscles. Innervation to the EDL was then examined, and signs of axonal degeneration were observed. It is suggested that aging is associated with alterations in the motor axon to the EDL muscle. These changes are manifest at the neuromuscular junction. In turn, the muscle responds as if it were in a state of functional denervation.     

Effect of nerve extract on atrophy of denervated or immobilized muscles

Changes in denervated muscles are due to disuse caused by paralysis of the muscle and the loss of special neurotrophic substances. We determined the relative roles of these two factors in the production of atrophy in denervated rats' extensor digitorum longus (EDL) muscles. Muscles were denervated and/or immobilized (by fixation of the ankle) for 7 days. Some rats also received daily intramuscular injections of a saline extract of rats' sciatic nerves (2.0 mg protein/ml). Atrophy was assessed by measurement of wet weight, total protein, and cross-sectional areas of types IIA and IIB fibers (in sections stained for ATPase). Both denervation and immobilization produced significant decreases in weight, protein, and areas of fiber. The group of rats with denervated EDL muscles had significantly greater atrophy than the group with immobilized muscles. In another group, denervated EDL muscles had significantly greater atrophy than contralateral muscles which were immobilized. However, when denervated muscles were injected with nerve extract, they did not differ significantly from contralateral, noninjected, immobilized muscles. Comparisons of the group of rats in which one EDL was denervated with groups in which one muscle was immobilized or was denervated and injected with nerve extract, indicated that loss of trophic influence was responsible for about 40% of the decreases in wet weight, total protein, and cross-sectional area of type IIB fibers, and the remaining 60% was due to disuse. Loss of trophic influence was responsible for only about 5% of the atrophy of denervated type IIA fibers. Therefore, inactivity and loss of neurotrophic influence were responsible for the atrophy which occurred in denervated skeletal muscles, and these two factors influenced the two types of fiber differently. The component of denervation atrophy due to loss of trophic influence could be completely prevented by injection of substances extracted from peripheral nerves.     

Glycosaminoglycans treatment increases IGF-I muscle levels and counteracts motor neuron death: A novel nonanticoagulant action

The present study shows that sciatic nerve crush in 2-day-old rats causes extensor digitorum longus (EDL) muscle atrophy and motor neuron loss and that treatment with glycosaminoglycans (GAGs) promotes muscle reinnervation, motor neuron survival, and markedly increases insulin-like growth factor-I (IGF-I) content in the denervated muscles. EDL muscle denervation-induced atrophy in saline-treated rats is progressive and reaches the greatest extent at 42 days after birth, which correlates with reduced EDL weight growth. There is also a partial reinnervation as shown by the number of reinnervated EDL muscle fibers (65.4% of control) and by the poor restoration of the indirect isometric twitch tension (62% of control) that is further reduced under tetanic stimulation (34% of control). The number of surviving motor neurons that innervate EDL muscle drops from 55 +/- 3 to 29 +/- 8. In GAGs-treated 42-day-old rats, the effects of neonatal nerve lesioning on EDL muscle atrophy and denervation are successfully reversed, and the isometric twitch tension and the capacity to hold tetanic stimulation are restored to almost control levels. The number of surviving EDL motor neurons is also increased to 43 +/- 4. Treatment with GAGs selectively affects IGF-I content in denervated hindlimb muscles, which is augmented from 7.02 +/- 0.71 ng/mg tissue to 25.72 +/- 0.7 in the EDL and from 3.2 +/- 0.18 to a robust 211 +/- 9.6 in the soleus.     

Putative effects of nerve extract on carbonic anhydrase III expression in rat muscles

Carbonic anhydrase III (CA III), the predominant CA isoform in skeletal muscle is very sensitive to neuronal influences. We aimed to determine whether CA III expression could be influenced by neurotrophic factor(s) present in sciatic nerve extract (SNE). Intact muscles were thus compared with denervated soleus (SOL), extensor digitorum longus (EDL), and tibialis anterior (TA) muscles injected daily for 7 days with saline solution (SS) or with SNE. CA III activity was significantly increased in SS-treated EDL and TA muscles compared to control (CTR), while SNE injections partially prevented this increase. There was no significant difference for CA III activity in the SOL between CTR, SS, and SNE groups. The CA III mRNA increase observed in response to denervation was reduced by 40% in SNE-treated EDL and TA muscles. While SOL CA III mRNA level was not affected by denervation, a 52% decrease was observed with SNE. We concluded that neuronal modulation of CA III expression in type II fibers may involve a neurotrophic component. © 1994 John Wiley & Sons, Inc.     

Potassium channels from normal and denervated mouse skeletal muscle fibers

The properties of singles K⁺ channels in normal and denervated muscles were compared using the “patch-clamp” technique. Single channels were recorded from vesicles obtained by stretching bundles of normal and denervated extensor digitorium longus (EDL) muscles. The most frequently observed channel in normal muscles was a high conductance (266 pS) Ca⁺⁺ activated K⁺ channel. Although channel density, as estimated by patch recording, showed a significant decrease in denervated muscles, no differences were found in conductance and gating properties. Another voltage-dependent K⁺ channel (81 pS) was only recorded from normal muscles, but never from denervated ones. In addition, a 35 pS conductance was recorded from both normal and denervated fibers. This channel displayed neither voltage dependence nor sensitivity to tetraethylammonium (TEA). In contrast, another TEA-insensitive (16 pS) channel was recorded only from denervated muscles. We conclude that denervation induces significant changes in the distribution and expression of K⁺ channels in mammalian skeletal muscles. © 1993 John Wiley & Sons, Inc.     

Observations on the effects of low frequency electrical stimulation on fast muscles of dystrophic mice.

The deterioration of tibialis anterior (TA) and extensor digitorum longus (EDL) muscles in dystrophic mice (C 57 BL dy/dy) was compared. The effects of chronic electrical stimulation on various characteristic properties of these muscles were also studied. The results indicate that EDL muscles are less affected by the disease than TA. This "selectivity" is difficult to explain since both muscles have similar fibre type composition. TA and EDL muscles that were stimulated for 10-28 days developed greater tetanic tensions than the contralateral muscles, but this effect was apparent only when the muscles were severely affected by the disease, that is the contralateral TA or EDL muscles developed less than 50% of the tension produced by muscles from normal animals. In all EDL muscles, stimulation increased the fatigue resistance. The time course of contraction and relaxation of dystrophic muscles is usually slower than that of normal muscles. The stimulation reduced this slowing effect, so that the stimulated muscles became similar to homologous muscles from normal littermates.     

Electrical stimulation increases matrix metalloproteinase-2 gene expression but does not change its activity in denervated rat muscle

Muscle-fiber atrophy occurs concomitantly with intramuscular connective tissue proliferation following denervation. These events contribute to the impairment of mechanical and functional properties of denervated muscles and compromise their recovery. Electrical stimulation (ES) is used in human rehabilitation to treat denervated muscles. However, the effects of this therapy on the intramuscular extracellular matrix (ECM) remain uncertain. Metalloproteinases (MMPs) are responsible by remodeling ECM in many neuromuscular disorders. This study evaluates the effect of ES on the activity of two important MMPs, MMP-2 and MMP-9, both involved in ECM remodeling of rat denervated muscles. Thirty-four Wistar rats (3 months old, 356 +/- 38.7 g) were divided into five groups: denervated (D); D+ES; sham denervation; normal (N); and N+ES. Twenty maximal muscle contractions were stimulated every 48 h using surface electrodes, as generally used in the rehabilitation of human denervated muscle. Both zymographic analysis and real-time polymerase chain reaction (PCR) of MMPs were used to evaluate muscle after denervation for 28 days. Both the D and D+ES groups showed increased MMP-2 activity compared with the N group (P < 0.05). Furthermore, only the D+ES had increased MMP-2 gene expression compared with the N group (P < 0.05). MMP-9 activity was not detected in any of the groups. The results of this study indicate that denervation increases MMP-2 activity, and ES regulates MMP-2 gene expression in rat denervated skeletal muscle. These findings clarify the effects of ES on the ECM of denervated muscle and may be helpful in designing new therapeutic strategies for rehabilitation in patients with denervation of muscle.     

Effect of denervation of neonatal rat sciatic nerve on the differentiation of myosin in a single muscle fiber

Myosin light chains in normal and neonatally denervated rat muscle were studied to examine the neural effect on the differentiation of myosin molecules. Those of fast- or slow-twitch muscle were identified by single fiber gel electrophoresis. Myosin light chains of rat soleus and extensor digitorum longus (EDL) muscles were converted to the fast type after neonatal denervation. In denervated EDL muscle, some hypertrophied intermediate fibers remained even after 30 days. Single fiber gel electrophoresis showed that slow and fast types of myosin light chains coexisted in these hypertrophied fibers.     

去神经对大鼠骨骼肌碳酸酐酶Ⅲ表达和磷酸酶活性的影响

目的 观察去神经对骨骼肌碳酸酐酶Ⅲ(carbonic anhydrase Ⅲ,CAⅢ)表达及其磷酸酶(phosphatase)活性的影响,探讨神经冲动受阻是否为重症肌无力(myasthenia gravis,MG)骨骼肌CAⅢ减少的原因.方法 定向切断支配大鼠趾长伸肌(extensor digitorum longus,EDL)和比目鱼肌(soleus,Sol)的神经纤维,术后第7、14、28和56天用Western blot分析EDL和Sol的CAⅢ水平,用固相膜上原位酶活性染色方法评估CAⅢ的磷酸酶活性.结果 (1)正常侧(即去神经对侧)Sol的CAⅢ水平远高于EDL,并且两者都表现出随时间增加(动物年龄增长)而增加的趋势.去神经后,EDL的CAⅢ水平随时间的延长而逐渐增加;Sol的CAⅢ水平则以14 d为分界先增加后降低.(2)正常侧Sol的CAⅢ的磷酸酶活性[随时间增加(动物年龄增长)呈逐渐增加的趋势]均高于EDL(变化不明显).去神经后,Sol的CAⅢ磷酸酶活性(第14、28、56天分别为14.39±1.93、11.48±1.46、9.04±1.46)明显低于正常侧(22.75±1.80、25.26±3.15、25.82±2.97,t=0.002、0.005、0.002,均P＜0.05),EDL的CAⅢ磷酸酶活性与正常侧相比亦是降低,但差异无统计学意义.(3)正常侧EDL和Sol的CAⅢ蛋白表达水平和CAⅢ的磷酸酶活性相一致;去神经后CAⅢ蛋白表达水平和CAⅢ的磷酸酶活性发生了背离,即CAⅢ蛋白表达水平增加,但其磷酸酶活性却降低.结论 去神经所致的神经冲动传递障碍与MG自身抗体所致的神经冲动传递障碍对骨骼肌CAⅢ表达水平的影响不同,MG骨骼肌CAⅢ表达水平减少并非是其自身抗体所致的神经冲动传递障碍造成.

Abstract：

Objective To observe the effects of nerve impulses on the expression of carbonic anhydrase Ⅲ ( CAⅢ ) and its phosphatase activity, and to explore whether or not the cause of CAⅢ expressive decreased in skeletal muscles of myasthenia gravis( MG) is resulted from the obstruction of nerve impulse.Methods The motor nerves of extensor digitorum longus (EDL, mainly composed by fast fibers) and soleus (Sol, mainly composed by slow fibers) were cut off by operation of denervation.Levels and phosphatase activities of CAⅢ were analyzed at 7, 14, 28, and 56 d after denervation by Western blot and specific enzyme staining on the membrane following SDS-polyacrylamide gel electrophoresis, respectively.Results (1) Levels of CAⅢ in Sol of normal side (eg denervated contralateral) were much higher than that in EDL of normal side, and the levels in both Sol and EDL had an enhanced tendency with time (age) increase, especially for Sol.After denervation, the levels of CAⅢ in EDL were gradual increased, however, the level in Sol was 14 d after denervation as the boundary of ascension and then decline.( 2) The phosphatase activities of CAⅢ in Sol of normal sides were much higher than that in EDL of normal sides, and there were an enhanced tendency with time (age) increase in Sol, but no significant changes were found in EDL The enzyme activities in denervated Sol were lower(in the 14, 28, and 56 days after denervation: 14.39 ±1.93, 11.48 ±1.46, 9.04 ±1.46) much than their contralaterals(22.75 ± 1.80, 25.26 ±3.15, 25.82 ± 2.97; t = 0.002, 0.005, 0.002, all P ＜ 0.05), the enzyme activities in denervated EDL were also lower than their contralaterals, however, no significant differences were found.(3)It was consistent for CAⅢ levels and phosphatase activities in both Sol and EDL of normal sides.After denervation, however, the deviation of the CAⅢ levels and phosphatase activities happened, the levels of CAⅢ were increased, but the phosphatase activities were decreased.Conclusions The effect of nerve impulse transferring obstructed by denervation on CAⅢ expression of skeletal muscles is different from that by MG auto-antibody.The decrease of CAⅢ protein in the MG muscles may be not resulted from the nerve impulse transferring obstructed by MG auto-antibody.     

Effect of electrotherapy on denervated muscles in rabbits: An electrophysiological and morphological study

The effects of electrotherapy on muscles denervated by crushing the sciatic nerve were studied in rabbits using electrophysiologic and morphologic techniques. The sciatic nerve was crushed in the thigh, just above its division into the lateral and medial popliteal nerves and the completeness of denervation was ascertained by EMG tests. Electrotherapy was carried out in six animals and six others were denervated controls; the contralateral leg of each animal was used as the normal control. The first appearance of signs of reinnervation was detected by means of EMG tests and the “reinnervation time” established. The animals were killed at the 50th day after nerve crush; the length of nerves below the crushed point was measured; soleus and extensor digitorum longus (EDL) muscles were removed and weighed. The percentages and the mean diameter of different muscle-fiber types in normal, control-denervated, and treated soleus and EDL muscles were calculated. No statistically significant difference was observed between electrophysiologic findings in control-denervated and treated rabbits. Electrotherapy was found to antagonize the weight loss of EDL muscles and the reduction of type 2b fiber diameters induced by denervation, but significantly accentuated the reduction of the mean diameter of type 1 fibers in EDL and soleus and increased the weight loss of denervated soleus muscles. The results obtained raise further doubts about the clinical utility of electrotherapy.     

A specific force deficit exists in skeletal muscle after partial denervation.

Skeletal muscle demonstrates a specific force deficit after repair of injured peripheral nerves, microneurovascular muscle transfer, and normal aging. Because atrophy cannot account for deficits in specific force, other, unknown, mechanisms are responsible for the resulting muscle contractile dysfunction under these circumstances. We tested the hypothesis that a subpopulation of denervated fibers is partially or completely responsible for the specific force deficit after partial denervation of the rat extensor digitorum longus muscle (EDL). Adult Fisher rats underwent either sham exposure or partial transection of 80% of the cross-sectional area of the left deep peroneal nerve. After a 2-week recovery period, maximum isometric force (F(0)) was measured in situ and maximum specific force (sF(0)) was calculated for EDL from both control (n = 8) and partial denervation (n = 7) groups. Innervated fiber cross-sectional area (CSA(inn)) was measured directly from whole EDL cross sections after immunohistochemical labeling for neural cell adhesion molecule (NCAM), a marker of muscle fiber denervation. A corrected specific force value (sF(0-inn)) was calculated by normalizing F(0) to CSA(inn). Partial skeletal muscle denervation resulted in significant reductions in muscle mass, F(0), and sF(0). The percentage of muscle fibers expressing NCAM in the extrajunctional sarcolemma increased from 1.0 +/- 0.8% in control to 49 +/- 15% in partially denervated EDL muscles. A 62.7% deficit in EDL specific force was observed after partial denervation. Denervated muscle fibers accounted for 59.3% of this deficit, but sF(0-inn) still differed significantly between control and partially denervated muscles, with a 25.5% difference between groups. In partially denervated muscles, the specific force deficit is partially but not fully explained by a subpopulation of noncontractile, denervated fibers.     

Effect of denervation on sarcolemmal proteins and glycoproteins of fast and slow mammalian skeletal muscle

We compared the protein and glycoprotein composition of a sarcolemmal membrane fraction isolated from normal and denervated rat extensor digitorum longus (EDL) and soleus muscles. Membranes from EDL and soleus muscles showed significantly different protein compositions. A relatively small number of glycoproteins, which were all minor proteins, accounted for the majority of concanavalin A (ConA) and Ricinus communis agglutinin (RCA120) binding. These glycoproteins appear to be common to EDL and soleus but bound different relative amounts of lectin in the two muscles. A large proportion of the ConA binding sites in EDL, but not soleus, were cryptic (not accessible by ConA unless the membrane structure was disrupted). Denervation had a differential effect on sarcolemma from the two muscles with EDL exhibiting large changes and soleus changing little if at all. Several major proteins changed their relative concentrations after denervation and the relative amount of RCA120 bound to the major glycoproteins also changed. The major ConA-binding glycoproteins did not change in either membrane but denervation resulted in the exposure of most of the cryptic ConA-binding sites in EDL membranes. Endogenous sialyl- and galactosyl-transferase activities in the membrane fractions significantly increased in EDL, but did not change in soleus, suggesting that the turnover of the glycoproteins is increased in EDL after denervation.     

Dynamics of nuclei of muscle fibers and connective tissue cells in normal and denervated rat muscles

The mitotic activity in muscles of growing rats and the effect of denervation were studied by means of continuous infusion of 5-bromo-2-deoxyuridine (BRDU). Denervated muscles after 10 weeks contained 20 to 60% fewer muscle nuclei than normal; BRDU labeled about 25% of the nuclei of normal soleus and extensor digitorum longus (EDL) and of denervated EDL muscles but only 5% in the denervated soleus muscle. Labeled nuclei persisted in denervated but not in normal muscles. After the main growth period, the turnover of myonuclei was at most 1 to 2% per week. The behavior of connective tissue nuclei was similar to that in muscle fibers. Infusion of BRDU had no effect on contractile properties. It is suggested that the exceptionally rapid atrophy of the denervated rat soleus associated with loss of satellite cells was due to loss of myonuclei and differentiation and fusion of satellite cells. The cause may possibly be that the phase of postdenervation fibrillation is shorter than in other muscles.     

Insulin effects in denervated and non-weight-bearing rat soleus muscle

Previous reports indicated that glucose uptake in denervated muscle is resistant to insulin, while in non-weight-bearing (unweighted) muscle this effect of insulin is enhanced. To extend the comparison of these differences, insulin effects on amino acid uptake and protein metabolism were studied in soleus muscles subjected to denervation or unweighting. Denervated muscle showed insulin resistance of both 2-deoxy[1,2-3H]glucose and alpha-[methyl-3H]aminoisobutyric acid uptake whereas unweighted muscle showed an increased or normal response, respectively. Atrophy was greater in denervated than in unweighted muscle, apparently due to faster protein degradation. The stimulation of protein synthesis and the inhibition of protein degradation by insulin was generally less in denervated than in unweighted muscle. Since metabolic measurements in denervated-unweighted muscles did not differ from those in denervated-weight-bearing muscles, effects of denervation must be independent of leg posture.