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PubMed2003

Denervated muscle fibers explain the deficit in specific force following reinnervation of the rat extensor digitorum longus muscle.

The authors tested the hypothesis that, after denervation and reinnervation of skeletal muscle, observed deficits in specific force can be completely attributed to the presence of denervated muscle fibers. The peroneal nerve innervating the extensor digitorum longus muscle in rats was sectioned and the distal stump was coapted to the proximal stump, allowing either a large number of motor axons (nonreduced, n = 12) or a drastically reduced number of axons access to the distal nerve stump (drastically reduced, n = 18). A control group of rats underwent exposure of the peroneal nerve, without transection, followed by wound closure (control, n = 9). Four months after the operation, the maximum tetanic isometric force (Fo) of the extensor digitorum longus muscle was measured in situ and the specific force (sFo) was calculated. Cross-sections of the muscles were labeled for neural cell adhesion molecule (NCAM) protein to distinguish between innervated and denervated muscle fibers. Compared with extensor digitorum longus muscles from rats in the control (295 +/- 11 kN/m2) and nonreduced (276 +/- 12 kN/m2) groups, sFo of the extensor digitorum longus muscles from animals in the drastically reduced group was decreased (227 +/- 15 kN/m2, p < 0.05). The percentage of denervated muscle fibers in the extensor digitorum longus muscles from animals in the drastically reduced group (18 +/- 3 percent) was significantly higher than in the control (3 +/- 1 percent) group, but not compared with the nonreduced (9 +/- 2 percent) group. After exclusion of the denervated fibers, sFo did not differ between extensor digitorum longus muscles from animals in the drastically reduced (270 +/- 20 kN/m2), nonreduced (301 +/- 13 kN/m2), or control (303 +/- 10 kN/m2) groups. The authors conclude that, under circumstances of denervation and rapid reinnervation, the decrease in sFo of muscle can be attributed to the presence of denervated muscle fibers.

Animals↗
PubMed2005

Evaluation of FES-induced knee joint moments in paraplegics with denervated muscles.

The pendulum test was applied to evaluate functional electrical stimulation (FES)-induced joint moments in paraplegics with denervated muscles. Therefore a manipulandum was connected to the knee joint and programmed to elicit gravity-induced leg oscillations. The FES-induced output torque was compensated for in order to keep the leg in a mean vertical position (knee angle 90 degrees ). A second-order dynamical model was applied to extract the elastic and viscous moments from the recorded leg oscillations. This model provided an almost adequate description of the relaxed and FES-contracted states. In the relaxed state the elastic moment was 15.3 +/- 2.37 Nm/rad and the viscous moment was 0.41 +/- 0.21 Nms/rad. The FES-induced elastic moment was 29.4 +/- 28.5 Nm/rad and the FES-induced viscous moment was 1.53 +/- 1.03 Nms/rad (N = 10, before FES-training).

Adult↗
PubMed1984

Denervated muscle flaps: mass and thickness changes following denervation.

It has been previously well documented in different animal models and different muscle groups that there is an early rapid loss, followed by stabilization, of muscle mass. This study supports the findings and, in addition, correlates the change in thickness with the change in weight after ligation of the thoracodorsal pedicle.

Animals↗
PubMed1988

The effects of electrical stimulation on denervated muscle using implantable electrodes.

This experimental study investigated the effects of continuous electrical stimulation on denervated muscle. The canine peroneal nerve was severed and repaired microsurgically, and the denervated extensor muscle group of the leg was stimulated continuously with an implantable electrode and pulse generator. EMG study, muscle force measurement, muscle weight measurement, histology, and histochemistry were performed to study the effect at eight weeks after the operation. Continuous electrical stimulation (pulse frequency 130 pps, burst rate approximately 1 train/min) was effective in decreasing muscle atrophy and in improving muscle force. These findings may have broader clinical applications.

Animals↗
PubMed1982

Electrical stimulation of denervated muscle prevents decreases in oxidative enzymes.

The influence of muscular contraction on the oxidative enzymes and the diameters of muscle fibers was investigated. Soleus muscles of guinea pigs were denervated for four weeks. The denervated fibers showed a reduction in the intensity of staining for beta-hydroxybutyrate dehydrogenase, cytochrome oxidase, succinate dehydrogenase, and NADH-dependent tetrazolium reductase. Denervation also resulted in a decrease in fiber diameter. Denervated soleus muscles were electrically stimulated to contract over a four-week period at a frequency normally received by slow contracting muscles. Electrical stimulation caused the stain intensity of histochemical reactions for oxidative enzymes to appear to be normal or greater than normal in 90% of the denervated fibers. Stimulation also caused 69% of the denervated fibers to be of normal or greater than normal size. The results demonstrate that contraction of denervated muscle by electrical stimulation prevents the loss of oxidative enzymes and the atrophy associated with denervation.

Adenosine Triphosphatases↗
PubMed2005

Quantitative ultrastructural changes in satellite cells of rats immobilized after soleus muscle denervation.

Quantitative ultrastructural evaluation of satellite cells (SCs) of rats immobilized for 7, 14, and 36 days after soleus muscle denervation was performed. Alterations in SCs of experimental animals concerned mainly the decrease in the size of cells and their nuclei, in the volume fractions of the nucleus and nucleolus, as well as in the number of ribosome-like structures. They suggest that immobilization which proceeded denervation caused a decline in cell activity. An increase in the volume fraction and number of endosome/lysosome-like structures, suggesting elevated processes of degradation was also observed. The changes occurred mainly in the period between 7 and 14 days after muscle denervation and immobilization. In all groups of experimental animals an increase in number of caveolae-like structures on both, inner (muscle fiber-facing) and outer (basal lamina-facing) sides of SCs was found. Thus, it is likely that SCs of denervated and immobilized rats are affected by signal molecules released by muscle fibers and/or other cell types present in muscle. A tendency in changes in SCs, observed in the present study, was similar to those which we noticed previously in denervated soleus muscle. However, immobilization after denervation aggravated some of the ultrastructural alterations or the changes appeared earlier.

Animals↗
PubMed1974

Membrane properties underlying spontaneous activity of denervated muscle fibres.

We have examined the events underlying the initiation of spontaneous action potentials (fibrillation) in fibres of previously denervated rat diaphragm maintained in organ culture for up to 10 days.1. Based on discharge pattern, two classes of spontaneously active fibres were found: rhythmically discharging fibres, and fibres in which action potentials occur at irregular intervals.2. Sites of action potentials initiation were located by exploration along the fibre length with two independent extracellular recording electrodes. The majority of sites of origin in both regular and irregular fibres were at the former end-plate zone; however, there was no region along the length that could not, at least in some fibres, be a site of origin.3. Intracellular recording at or near sites of origin of action potential discharge showed two types of initiating events. Irregularly discharging fibres were brought to threshold by discrete depolarizations of up to 15 mV in amplitude, while regularly occurring action potentials were associated with oscillations of the membrane potential.4. Discrete depolarizations (called fibrillatory origin potentials or f.o.p.s) at sites of origin in irregularly discharging fibres have the following properties: (a) random occurrence and nearly constant amplitude outside a refractory period during which both amplitude and probability of a second f.o.p. are reduced; (b) associated inward current flow which is localized to about 100 mum or less along the fibre length, and (c) dependence of amplitude and frequency on membrane potential.5. Oscillation of membrane potential found at sites of origin of action potential discharge in regular fibres also occurred locally along the fibre length and was sensitive to changes in membrane potential.6. Both f.o.p.s and oscillations of membrane potential were reversibly abolished by low Na(+)-Ringer fluid or tetrodotoxin.7. Neither type of initiating event was appreciably affected by concentrations of D-tubocurarine which blocked extrajunctional sensitivity to acetylcholine.8. We conclude that spontaneous action potentials under these conditions arise from a localized Na(+)-conductance change in the membrane of the active fibre; this conductance change is distinct from the increased Na(+)-conductance which follows the interaction of acetylcholine with its receptor. Spontaneous activity in single, denervated muscle fibres is cyclical and self-inhibiting (Purves & Sakmann, 1974); thus the Na(+)-conductance change underlying the initiation of spontaneous action potentials is affected by muscle fibre activity.

Action Potentials↗
PubMed1976

The effect of external calcium and magnesium ions on the response of denervated muscle to acetylcholine.

1. The effect of external Ca and Mg on the membrane depolarization and contracture of rat denervated muscle in response to acetylcholine, ACh, was studied. 2. Raising external Ca concentration reduced the rate of rise and the amplitude of the ACh contracture, and prolonged its time course. 3. Increasing external Ca reduced the membrane depolarization in response to ACh. The dose increment required to elicit depolarization in high Ca concentration increased with external Ca, and was greater for depolarization than for contracture. 4. External Mg was less effect than Ca in reducing ACh depolarization but was more effective in reducing contracture. In contrast to Ca, Mg did not alter the time course of relaxation. 5. It is concluded that external Ca has two opposing effects on the ACh contracture: one of stabilizing the membrane and the other of increasing intracellular Ca concentration. External Mg may interfere with Ca influx and hence reduce contractility.

Acetylcholine↗
PubMed1991

Mitochondrial adaptations in denervated muscle: relationship to muscle performance.

We have studied mitochondrial adaptations in muscle subject to chronic denervation, and their relationship to muscle performance, using a model of unilateral sciatic nerve denervation in rats over periods of 2, 5, 8, 14, 21, 28, 35, and 42 days (n = 5-9 rats/day). Time to peak tension (TPT), one-half relaxation time (1/2RT), and endurance performance were evaluated during in situ stimulation of denervated and contralateral gastrocnemius-plantaris muscles. Denervation led to a 70% decline in muscle mass after 42 days. TPT and 1/2RT increased 17 and 30%, respectively, indicating a transformation toward slower muscle. The activities of the enzymes cytochrome-c oxidase (CYTOX), succinate dehydrogenase, and citrate synthase were decreased by 8-14 days, and by 42 days these were 34-58% of control. The mitochondrial phospholipid cardiolipin was reduced earlier, by 5 days, and gradually decreased to 37% of control. Thus phospholipid removal appears to precede the loss of enzyme activity during decreases in mitochondrial content. Endurance performance was reduced in parallel with decreases in enzyme activity and cardiolipin. Cytochrome c mRNA levels decreased to 52% of control by 5 days. Denervation resulted in coordinated changes in mRNA levels encoding the nuclear-derived CYTOX subunit VIc and the mitochondrially derived CYTOX subunit III. However, changes in CYTOX activity did not always parallel alterations in subunit mRNA levels. Thus transcriptional and translational mechanisms operate in regulating mitochondrial gene expression during denervation.

Animals↗
PubMed1991

Cyclic AMP stabilizes the degradation of original junctional acetylcholine receptors in denervated muscle.

We used mouse diaphragm muscle in organ culture to study the stabilization of acetylcholine receptor (AChR) degradation at denervated neuromuscular junctions. After denervation, the degradation rate of the AChRs present prior to denervation (slowly degrading, or Rs, AChRs) accelerates from the predenervation degradation half-life (t1/2) of approximately 8-10 days to a t1/2 of approximately 2-3 days. We report that addition to the organ culture medium of pharmacological agents that elevate cytoplasmic cAMP levels (forskolin, dibutyryl cAMP, and 8-bromo-cAMP) reversed the change in t1/2 caused by denervation, whereas addition of 1,9-dideoxyforskolin, a forskolin analog that does not elevate cytoplasmic cAMP levels, did not reverse the effect of denervation. The degradation rate of AChRs in primary myotube cultures and that of the newly synthesized AChRs in denervated muscle were little affected by forskolin or dibutyryl cAMP. The possibility is raised that the modulation of Rs AChR degradation by innervation may be mediated by cAMP.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1998

The observation of transplanted embryonic motoneurons in the denervated muscles of adult rats.

OBJECTIVE: To observe the survival of embryonic motoneurons after they were transplanted into the denervated skeletal muscles and to find a new method to retard the atrophy of denervated muscles. METHODS: Dissociated embryonic motoneurons prelabled with 5-bromo-2'-deoxyuridine (Brdur) on the embryonic days 12 were injected into the denervated gastrocnemius muscles of adult rats. Then gastrocnemius muscles were processed with Nissl staining, acetylcholinesterase staining and Brdur immunocytochemical staining to show the implanted motoneurons at 9 and 22 weeks post-transplantation. Myofibrillar ATPase staining was used to show the morphology of muscle fibers. The rats in experimental group were implanted with embryonic motoneurons in the predenervation muscles, while the rats in control group were injected with just culture medium without motoneurons. RESULTS: Embryonic motoneurons survived, developed and extended long axons to form neuromuscular junctions with the denervated muscles. The differentiation of muscle fibers and fiber type grouping occurred among bigger fibers in experimental group. The transverse area was smaller and there was no apparent fiber type grouping in control group. CONCLUSIONS: Embryonic motoneurons can survive, develop and reinnervate denervated muscles after being transplanted into denervated muscles. It is worth further investigating on ameliorating the atrophy of denervated muscle.

Animals↗