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Postnatal development of the mouse temporal muscle and effects of a fine-grained diet on the muscle spindle.

The postnatal development of the mouse temporal muscle and effects of a fine-grained diet on muscle spindles were investigated. On d 25 after birth, 3 types of extrafusal muscle fibers could be distinguished on the basis of SDH activity, but not on the basis of their diameters. And in 50-d-old mice, 3 types of the muscle fibers had different diameters each other. In intrafusal muscle fibers, the postnatal changes of the SDH activity were similar to those of extrafusal muscle fibers, but the diameter distribution showed unimodal statistical distribution from 10th to 50th postnatal day. On the other hand, in control 180-d-old mice, 80 percent of muscle spindles in the temporal muscle had complete annulospiral endings, but the ratio of muscle spindles with complete annulospiral endings was decreased significantly in mice fed a fine-grained diet. The diet also decreased the diameter of the endings significantly. These results suggest that the main changes in the morphological and functional properties of the mouse temporal muscle occur in during and early after weaning period, and that normal mastication is needed to maintain the homeostatic condition of the mouse temporal muscle.

Animals↗

Alterations of muscle activities and jaw movements after blocking individual jaw-closing muscles in the miniature pig.

Although the inactivation or removal of motoneurones and muscles are known to affect development and growth of the craniofacial skeleton and masticatory muscles, the effect of these on functional activity patterns is not clear. The goal of this study was to evaluate the immediate responses of masticatory muscle activities to temporary nerve blocks of individual jaw-closing muscles. Nineteen experiments were made with four miniature pigs (Sus scrofa). Electromyograms of the masticatory muscles and jaw movements were recorded during natural chewing. Then, the function of individual jaw-closing muscles was removed unilaterally by local anaesthesia, and the recording repeated. The results showed a general increase in the activities of the other jaw-closing muscles, particularly those that were synergistic with the blocked muscle in producing lateral movements. Furthermore, the lateral pterygoid showed stronger activity, and accordingly the lateral movement was increased. Digastric muscle activity and the magnitude of jaw opening also tended to increase. Thus, the response to loss of a muscle is a strong, immediate compensation by synergists.

Animals↗

Effect of inspiratory muscle work on peripheral fatigue of locomotor muscles in healthy humans.

The work of breathing required during maximal exercise compromises blood flow to limb locomotor muscles and reduces exercise performance. We asked if force output of the inspiratory muscles affected exercise-induced peripheral fatigue of locomotor muscles. Eight male cyclists exercised at > or = 90% peak O2 uptake to exhaustion (CTRL). On a separate occasion, subjects exercised for the same duration and power output as CTRL (13.2 +/- 0.9 min, 292 W), but force output of the inspiratory muscles was reduced (-56% versus CTRL) using a proportional assist ventilator (PAV). Subjects also exercised to exhaustion (7.9 +/- 0.6 min, 292 W) while force output of the inspiratory muscles was increased (+80%versus CTRL) via inspiratory resistive loads (IRLs), and again for the same duration and power output with breathing unimpeded (IRL-CTRL). Quadriceps twitch force (Q(tw)), in response to supramaximal paired magnetic stimuli of the femoral nerve (1-100 Hz), was assessed pre- and at 2.5 through to 70 min postexercise. Immediately after CTRL exercise, Q(tw) was reduced -28 +/- 5% below pre-exercise baseline and this reduction was attenuated following PAV exercise (-20 +/- 5%; P < 0.05). Conversely, increasing the force output of the inspiratory muscles (IRL) exacerbated exercise-induced quadriceps muscle fatigue (Q(tw) = -12 +/- 8% IRL-CTRL versus-20 +/- 7% IRL; P < 0.05). Repeat studies between days showed that the effects of exercise per se, and of superimposed inspiratory muscle loading on quadriceps fatigue were highly reproducible. In conclusion, peripheral fatigue of locomotor muscles resulting from high-intensity sustained exercise is, in part, due to the accompanying high levels of respiratory muscle work.

Adult↗

Muscle-specific expression of insulin-like growth factor I counters muscle decline in mdx mice.

Duchenne muscular dystrophy is an X-linked degenerative disorder of muscle caused by the absence of the protein dystrophin. A major consequence of muscular dystrophy is that the normal regenerative capacity of skeletal muscle cannot compensate for increased susceptibility to damage, leading to repetitive cycles of degeneration-regeneration and ultimately resulting in the replacement of muscle fibers with fibrotic tissue. Because insulin-like growth factor I (IGF-I) has been shown to enhance muscle regeneration and protein synthetic pathways, we asked whether high levels of muscle-specific expression of IGF-I in mdx muscle could preserve muscle function in the diseased state. In transgenic mdx mice expressing mIgf-I (mdx:mIgf+/+), we showed that muscle mass increased by at least 40% leading to similar increases in force generation in extensor digitorum longus muscles compared with those from mdx mice. Diaphragms of transgenic mdx:mIgf+/+ exhibited significant hypertrophy and hyperplasia at all ages observed. Furthermore, the IGF-I expression significantly reduced the amount of fibrosis normally observed in diaphragms from aged mdx mice. Decreased myonecrosis was also observed in diaphragms and quadriceps from mdx:mIgf+/+ mice when compared with age-matched mdx animals. Finally, signaling pathways associated with muscle regeneration and protection against apoptosis were significantly elevated. These results suggest that a combination of promoting muscle regenerative capacity and preventing muscle necrosis could be an effective treatment for the secondary symptoms caused by the primary loss of dystrophin.

Animals↗

Comparison of the muscle fiber diameter and satellite cell frequency in human muscle biopsies.

Satellite cells are responsible for the formation of postnatal muscle fibers. The number, mitotic activity, and differentiation potential of satellite cells and the muscle fiber diameter are tightly regulated events in normal muscle. The signal that induces satellite cells to stop proliferation once the determined muscle fiber size has been reached in normal growth is not known. The aim of the present study was to determine whether a correlation exists between satellite cell frequency and muscle fiber diameter in human muscle disease. Muscle biopsies from 7 cases of Duchenne muscular dystrophy (DMD), 8 other muscular dystrophies, 23 cases of inflammatory myopathy, and 22 cases of neurogenic atrophy were examined. The satellite cell number was elevated in DMD and neurogenic atrophy but not in other muscular dystrophies or inflammatory myopathies. Nevertheless, in all the diseased muscles, but not in normal controls, there was a significantly higher relative frequency of satellite cells with increasing fiber diameter. It has been shown before that satellite cells show ultrastructural and autoradiographic signs of activation and proliferation in myopathic and neurogenic conditions. We assume that we are dealing with activated, not quiescent, satellite cells in diseased muscle and that under these conditions the fiber diameter does not represent a stop signal for satellite cells to proliferate. The data suggest that not only the number of satellite cells matters in diseased muscle, as has been shown before, but that it is their behavior that influences, at least in part, progress and severity of muscle diseases.

Adolescent↗

Smooth muscle myosin heavy chain isoforms and their role in muscle physiology.

Unlike vertebrate skeletal muscle, smooth muscle myosin heavy chain isoforms are encoded by a single gene. Alternative splicing of the primary transcript from a single gene generates four smooth muscle myosin heavy chain isoforms. These isoforms differ both at the carboxyl terminus (SM1 and SM2 isoforms) and at the amino terminus (SM-A and SM-B isoforms). The smooth muscle myosin heavy chain isoforms are differentially expressed during smooth muscle development and in different smooth muscle cell types. The mechanical properties of smooth muscle may be correlated with the myosin heavy chain content/isoform expression. However, the precise function of each smooth muscle myosin heavy chain isoform to muscle contraction remains to be determined. This review mainly focuses on the molecular basis of smooth muscle myosin heavy chain isoform diversity, its expression during development and disease, and its role in muscle physiology.

Amino Acid Sequence↗

Innervation of muscle receptors in the cross-reinnervated soleus muscle of the cat.

It has recently been reported (Gregory et al., J. Physiol., 331:367-383, 1982) that cutting a muscle nerve and letting it grow back into the muscle or cross-uniting the muscle with a foreign nerve results in major disruption of the normal response patterns of muscle spindles and tendon organs. Here we report observations on the structure of muscle receptors in cross-reinnervated and self-reinnervated soleus muscles in an attempt to detect abnormalities that might account for their disturbed function. Eight soleus muscles were reinnervated with the extensor digitorum longus nerve for periods up to 449 days and two were self-reinnervated. Following the physiological investigation, the muscle was fixed and stained according to the method of Barker and Ip (J. Physiol., 69:73P-74P, 1963). Spindles and tendon organs were teased from the muscle and photographed. In one cross-reinnervated muscle an attempt was made to isolate all receptors. About two-thirds of the normal number of spindles and tendon organs were found. Three categories of receptor were identified: normal, abnormal, and those having no visible nerve endings. There appeared to be little difference in degree of abnormality of receptors in self- and cross-reinnervated muscles. Of the 180 spindles, 3% were normal, 43% had no visible endings, and 54% had abnormal endings. Of 80 tendon organs, 38% were normally innervated, 33% were without visible innervation, and 29% had abnormal endings. We conclude that following long-term cross-reinnervation and self-reinnervation of soleus there is extensive disruption of the normal innervation pattern of both spindles and tendon organs which could account for their functional abnormalities.

Animals↗

Skeletal muscle development in normal and double-muscled cattle.

This study examined the effect of genotype on prenatal muscle development in both normal-muscled (NM) animals and in double-muscled (DM) animals harboring a mutation in the gene for myostatin that results in the production of a functionally inactive protein. The following muscle development parameters were analyzed at four gestational ages: muscle weight, fiber type, by both enzyme histochemistry and myosin heavy-chain (MHC) immunocytochemistry, and average fiber area. The weights of both M. vastus lateralis and M. vastus medialis were greater throughout prenatal development in the DM animals compared to NM. The percentage of type 1 muscle fibers initially declined with gestational age and subsequently increased in both NM and DM. The percentage of type 1 fibers was consistently lower in DM than in NM. A pattern of MHC isoform localization was shown in DM muscle that is indicative of a delay in muscle development relative to NM. Muscle fiber size was differentially regulated in NM and DM, depending on fiber type. Type 1 fibers were smaller in DM than NM in late gestation, while type 2 fibers were smaller throughout gestation. This study suggests that the inactivating myostatin mutation in DM animals may be associated with changes in both skeletal muscle fiber type and fiber size during bovine muscle development.

Animals↗

A commentary on muscle unit properties in cat hindlimb muscles.

A broad survey of muscle unit properties in 14 muscles of the cat hind limb is presented which emphasizes some general features of unit properties in mammalian muscles. A more detailed analysis of muscle unit properties in three muscles of the posterior compartment of the lower leg is then presented using Burke's tetrapartite (FF, FI or F (Int.), FR, and S) unit classification scheme. Our data on the properties of motor units in cat tibialis posterior (TP) have been compared to those generated by Burke and colleagues on units in flexor digitorum longus (FDL) and medial gastrocnemius (MG). In all three muscles, twitch contraction time was distinctly slower for type S units and specific tension outputs were substantially greater for type FF units than for type S units. The innervation ratios of type FR units were slightly lower than for type S units but the specific tension of the FR units was closer to FF units than to type S units. The FF units controlled 70-74% of the cumulative force output of each muscles, indicating a substantial capacity for powerful rapid contractions of all three of these muscles despite their differences in "size," action, and force generation. Distinctive features of the three muscles included differences in the unit types' force producing capabilities and in the relative representation of "nonfatigable" type FR and S units in each muscle. In particular, TP is endowed with some unusually powerful type FF units and a high percentage (42%) of type S units. In contrast, FDL has units that develop relatively little force and an unusually high representation (56%) of type FR units. The possible relationships between these muscle features and their presumed role in posture and locomotion is discussed.

Animals↗

Functional morphological interpretation of the distribution of muscle spindles in the jaw muscles of the mallard (Anas platyrhynchos).

The morphology and distribution of muscle spindles of jaw and tongue muscles in the mallard were examined in serial transverse sections of single muscles and in horizontal sections of a whole head. Our observations on spindle morphology are in agreement with previous descriptions of spindles in birds. Some spindles differ in their innervation and the pattern of intrafusal muscle fibers. The spindles of individual adductor and pterygoid muscles are distributed unevenly. Some adductor muscles lack spindles, whereas those of other muscles are confined to limited areas. Jaw opening muscles and extrinsic tongue muscles lack spindles. The stretch of extrafusal muscle fibers could be estimated from the difference in sarcomere length for birds with the beak open and closed. Not all muscle fiber groups are stretched evenly over the whole range of jaw opening. Only those fiber groups that are continuously stretched during jaw opening contain spindles.

Animals↗

Latency of skeletal muscle contraction after pulse train stimulation: an important factor in correct timing of skeletal muscle cardiac assist devices.

Various configurations of conditioned skeletal muscle are under investigation for cardiac assistance in patients with end-stage cardiac failure. Optimal timing of conditioned skeletal muscle contraction is essential for effective cardiac augmentation. However, unlike mechanical methods of assistance, skeletal muscle requires time to develop peak tension. We measured "time to 50% peak tension" and "time to 90% peak tension" using an electrical strain gauge in 12 canine latissimus dorsi muscles (6 untrained controls and 6 trained with 3 months of electrical stimulation at 25 Hz with a 15% duty cycle). The "time to 50% relaxation" and the "time to 90% relaxation" after discontinuation of the stimulus were also measured. Conditioned skeletal muscle required significantly more time to develop peak tension than unconditioned skeletal muscle. Relaxation was also significantly prolonged in conditioned muscle. Notably, conditioned lattisimus needed, on average, 0.35 sec to develop peak tension and 0.20 sec for 90% relaxation. Thus, 0.55 sec of each muscle contraction/relaxation cycle was devoted to development of peak tension and subsequent relaxation. At normal canine heart rates of approximately 120 beats per minute (0.50 sec per cardiac cycle), conditioned skeletal muscle may take up to 70% of each cardiac cycle (0.35 sec) to develop 90% of peak tension. The recognition of this phenomenon in conditioned skeletal muscle is important for effective contraction timing of both human and animal skeletal muscle assist devices. Development of proper conditioning regimens for such devices may benefit from identification of those training parameters which produce a minimal "time to peak tension."

Animals↗

Distinction between smooth muscle, fibroblasts and endothelial cells in culture by the use of fluoresceinated antibodies against smooth muscle actin.

FITC-labelled antibodies against native actin from chicken gizzard smooth muscle (Gröschel-Stewart et al., 1976) have been used to stain cultures of guinea-pig vas deferens and taenia coli, rabbit thoracic aorta, rat ventricle and chick skeletal muscle. The I-band of myofibrils of cardiac muscle cells and skeletal muscle myotubes stains intensely. In isolated smooth muscle cells, the staining is located exclusively on long, straight, non-interrupted fibrils which almost fill the cell. Smooth muscle cells which have undergone morphological "dedifferentiation" to resemble fibroblasts with both phase-contrast microscopy and electronmicroscopy still stain intensely with the actin antibody. In those muscle cultures which contain some fibroblasts or endothelial cells, the non-muscle cells are not stained with the actin antibody even when the reactions are carried out at 37 degrees C for 1 h or after glycerination. Prefusion skeletal muscle myoblasts also do not stain with this antibody. It is concluded that the actin antibody described in this report is directed against a particular sequence of amino acids in muscle actin which is not homologous with non-muscle actin. The usefulness of this antibody in determining the origin of cells in certain pathological conditions such as atherosclerosis is discussed.

Actins↗

The comparative effects of (Ca2+) and (Mg2+) on on tension generation in the fibers of skinned frog skeletal muscle and mechanically disrupted rat ventricular cardiac muscle.

The effects of intracellular Mg2+ on Ca2+-activated isometric tension generation in rat cardiac muscle fibers and frog skeletal muscle were compared. The membranous sarcolemmal barrier was removed from rat cardiac muscle fibers by mechanical disruption and from frog skeletal muscle by skinning. Tension was recorded in the fibers in bathing solutions of different Ca2+ concentrations and either 5 X 10(-5) M or 1 X 10(-3) M Mg2+ concentration (the same concentrations used in a previous study on single skinned frog skeletal muscle fibers [3]). The amount of Ca2+ required to activate the muscle increased with Mg2+ concentration for both rat ventricular muscle and frog skeletal muscle. These data indicate that intracellular Mg2+ concentration could strongly modulate Ca2+-activated tension in cardiac muscle and that very similar molecular mechanisms are responsible for Ca2+-activated tension in rat ventricular muscle and frog skeletal muscle. The possible sites of action of Mg2+ on Ca2+-activated tension are discussed.

Animals↗

The effects of different patterns of muscle activity on capillary density, mechanical properties and structure of slow and fast rabbit muscles.

When rabbit fast muscles were chronically stimulated at a frequency naturally occurring in nerves to slow muscles (10 Hz), there was a transformation towards a slow muscle type such as an increase of capillary density, increased activity of the oxidative enzyme, succinic dehydrogenase, and a decrease of muscle fibre diameters. After 28 days the intensity and distribution of SDH and the capillary density were similar to those of soleus. The increases in capillary density preceded the changes in activity of SDH; there was a significantly greater capillary/muscle fibre ratio and number of capillaries/mm2 in muscles stimulated for only 4 days at which time no change could be detected in SDH. These changes were induced by slow frequency stimulation only, and not by an overall increase of activity. Stimulation of fast muscles for 4 days at a higher frequency naturally occurring in the nerves to fast muscles (short bursts of tetani), with the same total number of stimuli as that used in slow frequency stimulation did not produce any changes in capillary density, activity of SDH or contraction times. No changes were observed in either fast or slow muscles stimulated with short bursts of tetani (and lower total number of impulses) up to 28 days. Activation of fast muscles at 5 Hz continuously or 10 Hz intermittently also caused an increase in capillary density. It is therefore concluded that only low frequency activation of fast muscles brings about a transformation of the muscle fibres towards a slow type and that the first noticeable change is an increase in the capillary density.

Animals↗

T-tubule endocytosis in dystrophic chicken muscle and its relation to muscle fiber degeneration.

Pectoralis muscles from normal and dystrophic chickens were investigated 2 h after an i.v. injection of horseradish peroxidase, by cytochemical and biochemical techniques to demonstrate peroxidase activity. Light microscopic examination of dystrophic muscles showed that peroxidase activity could be detected inside a population of fibers, in deliminated bodies often restricted to segments of the muscle fiber. Such bodies containing peroxidase were not observed in normal muscle fibers. Electron microscopy of dystrophic muscle fibers revealed that numerous vesicles containing peroxidase were frequently present in fiber regions with signs of cytoplasmic degradation. These vesicles, which occasionally were found to be coated, were 50--100 nm in size and appeared to be derived from t-tubules. Larger (up to 1.7 micrometers) inclusions containing peroxidase and delimited by a single membrane were also present at degenerating areas of dystrophic muscle fibers. These bodies seemed to be formed by fusion between several primary t-tubule vesicles and probably also lysosomes. Vacuoles containing the peroxidase were frequently encountered. Biochemical determination of horseradish peroxidase activity, performed after extensive washing of the muscle tissue, showed that dystrophic muscles contained about twice as much peroxidase as normal control muscles. It is suggested that endocytosis from t-tubules is an early and essential pathological phenomenon in dystrophic muscle fibers, which may be related to lysosomal function and muscle fiber degeneration

Animals↗

[Muscle physiology and the effect of muscle-tendon surgery in cerebral palsy].

The muscle reacts physiologically in neuromuscular disorders which do not affect muscle tissue directly (such as muscular dystrophies), and adapts to altered demands. For this reason, alterations in the muscle-tendon apparatus are grossly secondary. Changing load stimulates an increase in muscle fibres, whereas continuous pull results in an increase in collagen fibres (fibrosis). The length range in which a muscle produces force must be considered with respect to the range of motion of the joint in order to plan soft tissue corrections and to understand the postoperative result. An optimal correction of muscle length can increase muscle force whereas overlengthening will reduce it. The latter is desired in cases where spastic muscle force needs to be reduced. In contrast shortening the muscle-tendon apparatus may be indicated in order to correct overlength and to increase muscle force. The effect of intramuscular lengthening procedures, performed as an aponeurotomy or an intramuscular tenotomy, depends on the stretching program after surgery. Extramuscular tendon lengthening, on the other hand, results in an immediate length gain. The danger of overlengthening and consecutive muscle weakening, however, is greater with the tendinous procedures.

Animals↗

Extraocular muscle in merosin-deficient muscular dystrophy: cation homeostasis is maintained but is not mechanistic in muscle sparing.

Extraocular muscle is uniquely spared from damage in merosin-deficient congenital muscular dystrophy. Using a murine model, we have tested the hypothesis that the maintenance of calcium homeostasis is mechanistic in extraocular muscle protection. Atomic absorption spectroscopy has demonstrated a strong correlation between the perturbation of calcium homeostasis in hindlimb muscle that is severely damaged and the absence of changes in calcium in extraocular muscle. If, as in other skeletal muscles, extraocular muscle fibers are destabilized by merosin deficiency, we would expect an increase in total muscle calcium coupled with an adaptive response in the high capacity/speed of the sarcoplasmic reticulum of the eye muscle. However, we have not observed the expected increases in total muscle calcium content, Ca2+-ATPase activity, Na+/Ca2+ exchanger content, or smooth ER Ca2+-ATPase content that are predicted by this model. Instead, these results indicate that the increased membrane permeability that characterizes, and is potentially mechanistic in, myofiber degeneration in muscular dystrophy does not occur in merosin-deficient extraocular muscle. Thus, the high-capacity calcium-scavenging systems are not primarily responsible for extraocular muscle protection in muscular dystrophy.

Animals↗

There is selective accumulation of a growth factor in chicken skeletal muscle. II. Transferrin accumulation in dystrophic fast muscle.

Transferrin or a transferrin-like protein, with ability to stimulate myogenesis and terminal differentiation in vitro, is found in fast chicken muscle during embryonic development. After hatching, however, transferrin is no longer accumulated or is only weakly accumulated by fast muscles like the pectoralis major and the posterior latissimus dorsi but continues to be accumulated by slow muscles like the anterior latissimus dorsi. In congenic lines of chickens bearing the gene for muscular dystrophy, however, adult fast muscles do not lose the ability to accumulate transferrin. While transferrin is found selectively in adult normal and dystrophic muscle it does not appear to be synthesized by muscle cells. Immunocytochemical localization shows that transferrin is accumulated not so much by muscle fibers as it is by single cells in the muscle interstitial space. The relationship between transferrin presence and growth patterns in adult skeletal muscle is not currently understood but evidence suggests that transferrin stimulation of myogenesis observed in vitro may be mediated in vivo by non-muscle cells dwelling within the muscle interstitial space. These cells may act as transferrin-uptake sources for subsequent satellite cell stimulation.

Animals↗