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Effects of muscle activity and fiber composition on glucose transport and GLUT-4.

We examined glucose uptake and GLUT-4 in rat muscles [soleus (Sol), plantaris (PL), extensor digitorum longus (EDL), tibialis anterior, and the red and white gastrocnemius (WG)]. In the normally innervated perfused rat hindlimb muscles the proportion of oxidative fibers was highly correlated with the muscle's insulin-stimulated 3-O-methyl-D-glucose (3-MG) uptake (R2 = 0.78) and GLUT-4 content (r = 0.94). Insulin-stimulated 3-MG uptake and GLUT-4 were also highly correlated (R2 = 0.996). In 3-day denervated muscles, insulin-stimulated 3-MG uptake was reduced in all six muscles (-41 to -14.6%, P < 0.05), and GLUT-4 content was also reduced (-87.5 to -34.9%), except in the WG and EDL (P > 0.05). A very high correlation was observed between the decrements in GLUT-4 (%) and the decrements in 3-MG uptake (%; r = 0.99). The relatively greater loss in muscle activity (%) due to denervation in the Sol compared with the PL coincided with the reductions (%) in GLUT-4 and 3-MG uptake. These studies demonstrate that glucose uptake and GLUT-4 are regulated by insulin-independent means, namely the oxidative capacity of the muscle and the normal activity level of the muscle.

3-O-Methylglucose↗

Quantitation of an alpha subunit splicing intermediate: evidence for transcriptional activation in the control of acetylcholine receptor expression in denervated chick skeletal muscle.

We have investigated the mechanisms responsible for the increase in acetylcholine receptor subunit mRNAs during the induction of denervation supersensitivity in skeletal muscle. Using a cRNA probe specific for exon 7 (224 nucleotides; with flanking intron sequences of 105 nucleotides on the 3' end, and of 70 nucleotides on the 5' end) of the alpha subunit of the chicken muscle acetylcholine receptor gene, we were able to quantitate the concentration of mature alpha subunit mRNA and its precursor. In 3-wk-old chicks, the concentration of alpha subunit message in leg muscle was found to be 4.0 attomoles per microgram total RNA, and to increase 40-fold within 1 wk after section of the sciatic nerve. The molar ratio of precursor/mature mRNA, which was approximately 0.023 in innervated as well as denervated muscle, transiently rose to 0.047 at the beginning of the second postoperative day when mature message content increased 20-fold; the rise in precursor level preceded the increase in mature message content. These findings suggest that an accelerated rate of transcription of the message coding for the alpha subunit causes increased message content and the stimulation of receptor synthesis characteristic of denervated muscle.

Animals↗

[Effect of calcium antagonists on action potentials of muscle fibers in the warm-blooded].

The effect of the "calcium antagonist" D600 (5.10(-6)--1.10(-4) g/ml) on the amplitude, duration and rate of the rise (Vmax) on the action potential (AP) of mouse diaphragm muscle fibers were studied. To evoke and record the AP, a standard microelectrode technique was employed with two microelectrodes being inserted into the same fiber about 50 micrometer apart. The fibers were stimulated by a single pulse or by serial ones. D600 was shown to reduce the amplitude and Vmax of AP and to increase its duration both in innervated and denervated muscle fibers. The magnitude of the membrane potential and the input resistance were not affected by D600. After denervation the sensitivity of muscle fibers to D600 fell. In the course of stimulation applied by serial pulses (1--2 Hz) instead of single ones, the inhibitory effect of D600 drastically increased. It is suggested that D600 strongly modifies the activity of fast sodium channels, the manifestations of the effect being controlled by innervation.

Action Potentials↗

Transcutaneous neuromuscular electrical stimulation effect on the degree of microvascular perfusion in autonomically denervated rat skeletal muscle.

OBJECTIVE: To determine the effect of transcutaneous neuromuscular electrical stimulation (TNMES) on the degree of microvascular perfusion in autonomically denervated skeletal muscle. DESIGN: A completely randomized experimental design was used to compare the effects of TNMES on the degree of microvascular perfusion in the tibialis anterior (TA) and extensor digitorum longus (EDL) muscles from autonomically denervated rats (Ch-TES) to the degree of microvascular perfusion in the same muscles of untreated controls, rats receiving only TNMES (TES), and rats receiving only autonomic denervation (shams). INTERVENTION: All electrical stimulation treatments were delivered via carbon silicone surface electrodes, and evoked sustained tetanic contraction of the TA and EDL muscles. Autonomic denervation was achieved by the application of chlorisondamine. MAIN OUTCOME MEASURES: The degree of microvascular perfusion was determined for the deep (DTA) and superficial (STA) region of the TA muscle and the EDL muscle by calculating their perfused microvessel/muscle fiber (PV/F) ratio. RESULTS: The PV/F ratio in the DTA from Ch-TES animals was greater (p < or = .05) than that in the same muscle from control and sham animals. The PV/F ratios in the STA and EDL from Ch-TES animals were not significantly (p > .05) different from the PV/F ratio in the respective muscles of shams. CONCLUSIONS: The response of the microvasculature in autonomically denervated skeletal muscle to TNMES that evokes muscle contraction is variable, and (2) mechanisms other than autonomic regulation may be involved in this hyperemic response.

Analysis of Variance↗

Physiologic basis of potentials recorded in electromyography.

The extracellularly recorded configuration of a single muscle fiber discharge is generally appreciated to be triphasic with an initially positive deflection. However, careful attention to waveform appearance during the electrodiagnostic medicine examination reveals that both innervated and denervated muscle waveforms may display a pantheon of configurations. Further, despite the fact that innervated and denervated single muscle fiber discharges arise from distinctly different intracellular action potential (IAP) configurations, their extracellularly recorded waveforms can appear quite similar, leading to potential misidentification and, hence, the possibility of an erroneous diagnostic conclusion. The least appreciated, but nevertheless critical, aspect of explanations for muscle waveform configurations is the relationship between the muscle fiber and recording electrode. Additionally, it is important to appreciate both the near-field and far-field aspects of single fiber and compound muscle action potentials. In this review, the leading/trailing dipole model is used to explain muscle waveform configurations in both innervated and denervated tissues.

Electromyography↗

The kinematics and mechanism of prey capture in the African pig-nosed frog (Hemisus marmoratum): description of a radically divergent anuran tongue.

High-speed videography and muscle denervation experiments were used to quantify the feeding kinematics of Hemisus marmoratum and to test hypotheses of muscle function. The feeding behavior of H. marmoratum, which feeds on ants and termites, differs radically from that of other frogs that have been studied. During feeding in H. marmoratum, the tongue 'telescopes' straight out of the mouth, as opposed to the 'flipping' tongue trajectory observed in most other frogs. At the time of prey contact, two lateral lobes of tissue at the tongue tip envelop the prey. These lateral lobes are capable of applying significant pulling forces to the prey and the tongue is, therefore, described as prehensile. The trajectory of the tongue can be adjusted throughout protraction so that the frog can 'aim' its tongue in all three dimensions; distance, azimuth and elevation. Bilateral denervation of the genioglossus muscles results in a complete lack of tongue protraction, indicating that the genioglossus muscle is the main tongue protractor in H. marmoratum, as in other frogs. Thus, H. marmoratum provides strong evidence of functional conservatism of the genioglossus muscle within anurans. Bilateral denervation of the hyoglossus muscle indicates that although the hyoglossus is involved in several aspects of normal tongue retraction, including the prehensile capability of the tongue tip, it is not necessary for tongue retraction. Unilateral denervation of the genioglossus muscle causes significant deviation of the tongue towards the denervated side, providing evidence for a mechanism of lateral tongue aiming. On the basis of the kinematics of prey capture, the anatomy of the tongue and the results of the denervation experiments, we propose that H. marmoratum uses a hydraulic mechanism to protract its tongue.

Animals↗

Expression of functional alpha7 nicotinic acetylcholine receptor during mammalian muscle development and denervation.

We have studied, on the transcriptional, protein and functional level, the expression of alpha7 nicotinic acetylcholine receptors (nAChR) in the course of rat muscle development, denervation and renervation. At foetal day 13, alpha7 nAChR expression was observed in somites and developing muscles of the back, but not yet in migrating myoblasts. Two days later, concomitant with myoblast aggregation, the alpha7 isoform began to be expressed in isolated myoblasts, with the highest level of expression in the frontal zone of the migrating wave. On foetal day 18, a time when the myoblasts in the upper hindleg have fused, alpha7 nAChR expression was most prominent in the outer layer of muscle tissue. The highest level of expression was observed in the first postnatal week, when practically all muscle cells stained positively for alpha7 protein. During the following weeks, alpha7 nAChR expression slowly decreased and practically disappeared in adult hindleg muscle. Following chronic denervation of adult Soleus muscle fibres, expression of alpha7 nAChR returned within 2-4 weeks. Electrophysiological measurements showed that the alpha7 nAChR of chronically denervated soleus muscle fibres were functional and, in particular, that they could be activated by choline. The presence of the alpha7 nAChR in developing and denervated muscle suggests a role for this nicotinic receptor in neuronal pathfinding and/or endplate stabilization.

Animals↗

Transient and chronic neonatal denervation of murine muscle: a procedure to modify the phenotypic expression of muscular dystrophy.

The extensor digitorum longus muscles of 14-d-old normal (129 ReJ ++) and dystrophic (129 ReJ dy/dy) mice were denervated by cutting the sciatic nerve. One denervation protocol was designed to inhibit reinnervation of the shank muscles, the other to promote reinnervation. Chronically denervated muscles (muscles that remained denervated for 100 d after nerve section) exhibited marked atrophy, but the number of myofibers in these muscles (1066 +/- 46 and 931 +/- 62 for the denervated normal and dystrophic muscles, respectively) was similar to the number of myofibers found in age-matched, unoperated normal muscles [922 +/- 28 (Ontell et al., 1984)] and was significantly greater than the number of myofibers found in age-matched dystrophic muscles [547 +/- 45 (Ontell et al., 1984)]. Similar effects on myofiber number were obtained when denervated muscles were allowed to reinnervate. Reinnervation of both normal and dystrophic muscles mitigated the marked atrophy that characterized chronically denervated muscles. The dystrophic reinnervated muscles appeared "healthier" than age-matched, unoperated dystrophic muscles, having 70% more myofibers, less myofiber diameter variability, substantially less connective tissue infiltration, and a greater amount of contractile tissue at their widest girths. The present study demonstrated that it is possible to alter the phenotypic expression of the histopathological changes associated with murine dystrophy, in dystrophic myofibers that are formed during fetal development, by subjecting the muscle to neonatal denervation.

Animals↗

[Effective treatment of a large muscle hernia by local botulinum toxin administration].

A 53-year-old patient developed an impairing muscle hernia when a fascia lata graft was harvested as a substitute for a cruciate ligament of the knee and closure of the defect was not possible. The fascial defect enlarged with time, extending along the whole upper leg. The large muscle protrusion and incarceration in the distal fascial slit was extremely painful during walking and getting up from a chair. Since autologous grafts were disregarded because of the high tissue pressure and alloplastic substitutes seemed problematic, the large hernia was successfully reduced by local muscle denervation with injections of botulinum-A toxin into the protruding vastus lateralis muscle. This procedure achieved relief of pain and enabled the patient to walk without complaints. Side effects were not observed.

Botulinum Toxins, Type A↗

The middle ear muscle of frogs does not modulate tympanic responses to sound.

The effect of the opercularis (= middle ear) muscle on the acoustic responsiveness of the tympanic middle ear of anuran amphibians was studied using laser vibrometric measurements of tympanic responses to sound. Removal of the muscle or direct stimulation of denervated muscles had no measurable effects on tympanic responses to sound in either American bullfrogs (Rana catesbeiana) or green treefrogs (Hyla cinerea) at any frequency or at any sound-pressure level studied. These results suggest that, contrary to proposed hypotheses, the opercularis muscle of the anuran middle ear is not capable of modulating the responsiveness of the tympanic middle ear. Instead, the opercularis system most likely functions as an independent system involved in acoustic reception.

Acoustic Stimulation↗

MR imaging features of radial tunnel syndrome: initial experience.

PURPOSE: To retrospectively assess magnetic resonance (MR) imaging features of radial tunnel syndrome. MATERIALS AND METHODS: Institutional review board approval was obtained, and informed consent was waived for the retrospective HIPAA-compliant study. MR images of 10 asymptomatic volunteers (six men, four women; mean age, 30 years) and 25 patients (11 men, 14 women; mean age, 49 years) clinically suspected of having radial tunnel syndrome were reviewed for morphologic and signal intensity alterations of the posterior interosseous nerve and adjacent soft-tissue structures. MR images of the asymptomatic volunteers were reviewed to establish the normal appearance of the radial tunnel. MR images of the symptomatic patients were evaluated for the following: signal intensity alteration and morphologic alteration of the posterior interosseous nerve; the presence of mass effect on the posterior interosseous nerve such as the presence of bursae, a thickened leading edge of the extensor carpi radialis brevis, or prominent radial recurrent vessels; signal intensity alteration within the depicted forearm musculature such as edema or atrophy; and signal intensity changes at the origin of the common extensor and common flexor tendons, which would suggest a diagnosis of epicondylitis. RESULTS: All images of volunteers demonstrated normal morphology and signal intensity within the posterior interosseous nerve and adjacent soft tissues. Two volunteers had borderline thickening of the leading edge of the extensor carpi radialis brevis. Thirteen patients (52%) had denervation edema or atrophy within muscles (supinator and extensors) innervated by the posterior interosseous nerve. One patient had isolated pronator teres edema. Seven (28%) patients had the following mass effects along the posterior interosseous nerve: thickened leading edge of the extensor carpi radialis brevis (n = 4), prominent radial recurrent vessels (n = 1), schwannoma (n = 1), or bicipitoradial bursa (n = 1). The rest of the patients had either normal MR imaging findings (n = 4) or lateral epicondylitis (n = 2). CONCLUSION: Muscle denervation edema or atrophy along the distribution of the posterior interosseous nerve is the most common MR finding in radial tunnel syndrome.

Adult↗

Desensitization of the acetylcholine receptor of denervated rat soleus muscle and the effect of calcium.

1 Desensitization of the extrajunctional acetylcholine receptors of denervated rat soleus muscle has been studied by evoking iontophoretic acetylcholine potentials at a high frequency (10 Hz). 2 Desensitization occurred with a slow and at least one fast component. 3 Increasing the dose of acetylcholine decreased the half time of onset of desensitization, but did not alter recovery half time. 4 Alteration of external calcium between 0 and 50 mM, or perfusion with agents which increase intracellular calcium such as 2,4-dinitrophenol and the calcium ionophores, X537A and A23187, did not alter desensitization half time. 5 The cholinoceptor agonists acetylcholine, acetylthiocholine, tetramethylammonium and phenyltrimethylammonium all caused desensitization at the same rate.

Acetylcholine↗

Differential effects of succinylcholine and acetylcholine on endplate and extrajunctional membranes of normal and denervated mouse skeletal muscle fibres.

Depolarization provoked by 10(-7)-10(-4) succinylcholine (SCh) and acetylcholine (ACh) was measured in thin bundles dissected from normal and 1-15 days denervated mouse muscles using the microelectrode technique. The muscles were superfused by Cl- -free solutions containing 30 mM K+ to prevent contracture responses. In endplate areas of normal muscles, sensitivity to SCh was roughly 10 times higher than the sensitivity to ACh. By contrast, the extrajunctional membrane of chronically denervated muscles was less sensitive to SCh than to ACh by about the same factor. The extrajunctional membrane of non-denervated soleus muscles was also more sensitive to ACh than to SCh but, unlike the response of the denervated membrane, the depolarization was transient.

Acetylcholine↗

Tetrodotoxin prevents motor unit enlargement after partial denervation in rat hindlimb muscles.

Findings that increased neuromuscular activity significantly reduced sprouting in partially denervated muscles prompted this present study to determine if the converse is true, namely that reduced activity promotes sprouting and motor unit (MU) enlargement. Partial denervation of rat hindlimb muscles by either the L4 or L5 spinal root avulsion resulted in extensive denervation (> 80 %) in tibialis anterior (TA) and medial gastrocnemius (MG) muscles, and moderate denervation (~50 %) in soleus (SOL) and plantaris (PL) muscles. The partially denervated muscles were then subjected to a 4 week programme of normal caged activity or TTX-induced neuromuscular inactivity. At 1 month, measurement of MU enlargement and quantification of sprouting were evaluated, respectively, by electrophysiological and histochemical means. Analysis of electrophysiological data showed that MU forces were significantly increased in both extensively and moderately denervated muscles 1 month after partial denervation and normal cage activity and that neuromuscular activity blockade by TTX completely abolished the MU enlargement in these partially denervated muscles. Histochemical analysis of sprouting revealed that the number of sprouts was significantly increased after partial denervation and normal cage activity, particularly after extensive denervation. TTX-induced neuromuscular inactivity dramatically reduced the number of sprouts and increased the number of free endplates in the extensively but not the moderately denervated muscles. These data demonstrate that a reduction in neuromuscular activity mediated by presynaptic blockade of neural action potentials reduces MU enlargement in partially denervated muscles by reducing axonal sprouting.

Anesthetics, Local↗

Effects of long-term denervation on skeletal muscle in old rats.

We compared the reactions to denervation of limb muscles between young adult and old rats. After denervation for up to 4 months in 24-month-old rats, limb muscles were removed and analyzed for contractile properties, morphology, and levels of several key molecules, including the peptide elongation factors eEF1A-1 and eEF1A-2/S1, myogenin, gamma-subunit of the acetylcholine receptor, and cyclin D3. The principal difference between denervated old and young muscle is a somewhat slower rate of atrophy in denervated older muscle, especially among the type II fibers. Expression levels of certain molecules were higher in old than in young control muscle, but after denervation, levels of these molecules increased to the same absolute values in both young and old rats. Although many aspects of postdenervation reactions do not differ greatly between young and old animals, the lesser degree of atrophy in the old rats may reflect significant age-based mechanisms.

Age Factors↗

Inhibition of insulin-stimulated xylose uptake in denervated rat soleus muscle: a post-receptor effect.

Insulin (100 U/l) stimulated xylose uptake in rat soleus muscle from a basal value of 2.3 +/- 0.5 to 11.6 +/- 2.1 mumol . g-1 . h-1. Denervation (section of the sciatic nerve) markedly reduced the stimulatory action of insulin (basal 1.3 +/- 0.4 mumol . g-1 . h-1; insulin-stimulated 4.5 +/- 0.6 mumol . g-1 . h-1). This effect appeared 3 days after denervation and was maximal after 5 days. Denervation also affected the insulin dose response curve; there was no effect of insulin in denervated muscle until the concentration exceeded 1 U/l. Denervation inhibited insulin-stimulated alpha-aminoisobutyrate uptake by 77% but did not affect 125I-insulin binding or glucose-independent activation of glycogen synthase by insulin. There was no effect of denervation on the insulinomimetic effects of concanavalin A, hydrogen peroxide, vitamin K5, anoxia, 2:4-dinitrophenol, cooling, hyperosmolarity or EDTA, but the effect of diamide was inhibited. It is concluded [1] that denervation inhibits insulin-stimulated sugar transport at some early post-receptor step, and [2] that the mechanism whereby insulin activates glycogen synthase is different from the activation of the membrane transport of sugars and amino acids.

Aminoisobutyric Acids↗

Turnover of acetylcholinesterase in innervated and denervated rat diaphragm.

The acetylcholinesterase (AChE) in rat diaphragms was labelled by intravenous injection of echothiophate in order to evaluate the turnover of AChE in innervated and denervated muscle in vivo. Echothiophate diethylphosphorylates AChE thereby inactivating it. Labelled (diethylphosphorylated) enzyme is rapidly and quantitatively reactivated with 1-methyl-2-hydroxyiminomethylpyridinium (2-PAM), so labelled (diethylphosphorylated) AChE was conveniently measured as 2-PAM-reactivatable AChE activity. In homogenates in vitro, label is lost spontaneously (diethylphosphorylated AChE spontaneously reactivates) with a half-time of 27 h. In innervated diaphragm, labelled non-end-plate AChE is lost with a half-time of 13 h. When correction is made for the spontaneous loss of label on the basis of in vitro measurements, this data indicates that non-end-plate AChE turns over with a half-time of about 26 h. In innervated diaphragm, labelled end-plate-specific AChE is lost more slowly than non-end-plate AChE and at a rate essentially identical to the rate of spontaneous loss of label in vitro. The rate of loss of labelled non-end-plate AChE is essentially identical in 18 h denervated and in paired innervated diaphragms. The rate of loss of labelled end-plate-specific AChE is significantly faster in 18 h denervated diaphragms than in paired innervated diaphragms. On the basis of these observations, hypotheses concerning the mechanisms of the denervation-induced decreases in non-end-plate and end-plate-specific AChE are formulated and discussed.

Acetylcholinesterase↗

[Skeletal muscle nuclear ATPase under denervation].

Denervation of the rabbit gastrocnemius muscle is shown to result after 18 and 72 h in a decrease of Mg2+-, Ca2+-dependent and an increase of Mg+-dependent parts of nuclear ATPase activity, with the total level of the enzyme activity retained. 7 days later the total ATPase activity of nuclei decreases as well as the expense of its EGTA-dependent part. These changes correlate with those in the nuclear Ca total content. Indirect electrostimulation of the denervated muscle increase both the 7g2+-, Ca2+-dependent ATPase activity and the Ca content in nuclei. Tenotomy for 18 h does not change these parameters.

Adenosine Triphosphatases↗