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PubMed1999

M-cadherin and its sisters in development of striated muscle.

Cadherins are calcium-dependent, transmembrane intercellular adhesion proteins with morphoregulatory functions in the development and maintenance of tissues. In the development of striated muscle, the expression and function of mainly M-, N-, and R-cadherin has been studied so far. While these three cadherins are expressed in skeletal muscle cells, of these only N-cadherin is expressed in cardiac muscle. In this review, M-, N-, and R-cadherin are discussed as important players in the terminal differentiation and possibly also in the commitment of skeletal muscle cells. Furthermore, reports are described which evaluate the essential role of N-cadherin in the formation of heart tissue.

Animals↗
PubMed1998

Developmental regulation of the serpin, protease nexin I, localization during activity-dependent polyneuronal synapse elimination in mouse skeletal muscle.

During vertebrate neuromuscular development, all muscle fibers are transiently innervated by more than one neuron. Among the numerous factors shown to potentially influence the passage from poly- to mononeuronal innervation, serine proteases and their inhibitors appear to play important roles. In this regard, protease nexin I (PNI), a potent inhibitor of the serine protease, thrombin, is highly localized to the neuromuscular junction (NMJ). In turn, thrombin is responsible for activity-dependent synapse elimination both in an in vitro model, and in vivo. In the present study, we used a monospecific anti-PNI polyclonal antibody to study the developmental kinetics of PNI expression in mouse leg skeletal muscle. By using immunoblotting, we detected PNI at embryonic day 16 (E16), as a 48-kDa band. This 48-kDa PNI band became prominent in leg muscle extracts at postnatal day 5 (P5) and remained so in extracts from adult muscle. In contrast, a higher molecular weight immunoreactive PNI band, which was sodium dodecyl sulfate- and beta-mercaptoethanol-resistant, was first detected at E16, increased at birth (P0), and then decreased at P15, i.e., after the wave of polyneuronal synapse elimination had occurred in these muscles. The results of an enzyme-linked immunosorbent assay, measuring active, complexed, and truncated PNI, correlated with Western blot data. We used immunocytochemistry to probe the localization of PNI at the NMJ and found that PNI was present in the cytoplasm of myotubes at E16, but neither then nor at birth did it colocalize with acetylcholine receptors. PNI became localized at NMJs by P5 and increased by P15, after which it remained stably concentrated there in the adult. Finally, we studied the gene expression of PNI mRNA, by using Northern blotting, and showed that PNI mRNA was present in skeletal muscle and remained stable throughout the time-course studies, suggesting that developmental regulation of muscle PNI occurs principally at the translational and/or post-translational levels. These results suggest that the localization of PNI, through a binding site or "receptor" may play an important role in differentiation and maintenance of synapse.

Aging↗
PubMed1994

Origin and development of the muscles of the intermetacarpal space of the forelimb of Felis catus.

This paper demonstrates the structure and development of the layer of mm. flexores breves profundi in Felis catus (Carnivora). By microdissections of the deep palmar musculature, it was found that there were formed two muscle layers: 1) four muscles beginning on the palmar side of the carpus, passing distally through the intermetacarpal spaces and inserting into the dorsal digital aponeurosis of the second to fourth digit--the superficial muscle layer of mm. flexores breves profundi; 2) four muscles beginning on the palmar area of the second to fifth metacarpus and inserting into the capsules of the metacarpophalangeal joints of the second to fifth digit--the deep muscle layer of mm. flexores breves profundi. Ontogenesis of these muscle layers was studied on 35 histological series of embryonal extremities. In early ontogenesis we found a coherent cell condensate of the anlage of mm. flexores breves profundi layer. Differentiation of the anlagen of individual muscles takes place in the foetuses of 17-20 mm crown-rump length. In embryos of 17-19 mm crown-rump length a small cell condensations corresponding to the layer of mm. intermetacarpales anlagen were found in the second and third intermetacarpal spaces. Both anlagen are formed only temporarily whereafter they break into fragments and extinct.

Animals↗
PubMed1998

Signalling by the Drosophila epidermal growth factor receptor is required for the specification and diversification of embryonic muscle progenitors.

Muscle development initiates in the Drosophila embryo with the segregation of single progenitor cells, from which a complete set of myofibres arises. Each progenitor is assigned a unique fate, characterized by the expression of particular identity genes. We now demonstrate that the Drosophila epidermal growth factor receptor provides an inductive signal for the specification of a large subset of muscle progenitors. In the absence of the receptor or its ligand, SPITZ, specific progenitors fail to segregate. The resulting unspecified mesodermal cells undergo programmed cell death. In contrast, receptor hyperactivation generates supernumerary progenitors, as well as the duplication of at least one SPITZ-dependent myofibre. The development of individual muscles is differentially sensitive to variations in the level of signalling by the epidermal growth factor receptor. Such graded myogenic effects can be influenced by alterations in the functions of Star and rhomboid. In addition, muscle patterning is dependent on the generation of a spatially restricted, activating SPITZ signal, a process that may rely on the localized mesodermal expression of RHOMBOID. Thus, the epidermal growth factor receptor contributes both to muscle progenitor specification and to the diversification of muscle identities.

Animals↗
PubMed1988

Ontogeny of architectural complexity in embryonic quail visceral arch muscles.

Understanding the mechanisms of muscle pattern formation requires that the complete sequence of ontogenetic events be defined, particularly in the emergence of architectural complexity and in the spatial relations between muscles and skeletal elements. This analysis of visceral arch myogenesis in quail (Coturnix coturnix japonica) embryos identifies the location of premuscle condensations and subsequent segregation of individual muscles, documents the initial orientation of myofibers and changes in alignment associated with maturation, and describes the spatial and temporal relations between muscle development and the formation of connective tissues. Premuscle condensations form within the visceral arches on embryonic days 2-4, before skeletal elements make their appearance. Discrete muscles may form from the subdivision of a muscle mass after fiber orientations have been established (e.g., jaw adductor and hyobranchial muscles) or by the segregation of a mesenchymal cluster from the condensation prior to the appearance of oriented fibers (e.g., protractor, muscle of the columella). The rate and pattern of subsequent muscle maturation are closely associated with the development of the hard tissues. Myogenesis in 4-9-day embryos centers around the quadrate cartilage, the retroarticular process of the mandibular (Meckel's) cartilage, and the epibranchial cartilage. Muscles form attachments on these elements and remain without additional attachments until the appropriate elements (e.g., otic capsule, pterygoid bone) develop. No single description of myogenic events applies to all visceral arch muscles, nor is there an arch-specific pattern of ontogeny. Rather, each muscle has distinctive characteristics based on its spatial relations within the developing head.

Animals↗
PubMed1995

Involvement of transglutaminase in myofibril assembly of chick embryonic myoblasts in culture.

Involvement of transglutaminase in myofibrillogenesis of chick embryonic myoblasts has been investigated in vitro. Both the activity and protein level of transglutaminase initially decreased to a minimal level at the time of burst of myoblast fusion but gradually increased thereafter. The localization of transglutaminase underwent a dramatic change from the whole cytoplasm in a diffuse pattern to the cross-striated sarcomeric A band, being strictly colocalized with the myosin thick filaments. For a brief period prior to the appearance of cross-striation, transglutaminase was localized in nonstriated filamental structures that coincided with the stress fiber-like structures. When 12-o-tetradecanoyl phorbol acetate was added to muscle cell cultures to induce the sequential disassembly of thin and thick filaments, transglutaminase was strictly colocalized with the myosin thick filaments even in the myosacs, of which most of the thin filaments were disrupted. Moreover, monodansylcadaverine, a competitive inhibitor of transglutaminase, reversibly inhibited the myofibril maturation. In addition, myosin heavy chain behaved as one of the potential intracellular substrates for transglutaminase. The cross-linked myosin complex constituted approximately 5% of the total Triton X-100-insoluble pool of myosin molecules in developing muscle cells, and its level was reduced to below 1% upon treatment with monodansylcadaverine. These results suggest that transglutaminase plays a crucial role in myofibrillogenesis of developing chick skeletal muscle.

Animals↗
PubMedDate not supplied

[Characteristics of functioning of electromechanical coupling in striated muscles of higher and lower vertebrates].

A comparative pharmacological analysis of relative contributions of different signal transduction pathways in the activation of contraction (excitation-contraction coupling, ECC) in intact fast striated muscles of frog and lamprey was performed. It was found that the major mechanism responsible for the ECC in muscles of both animals is Ca2+ release from the sarcoplasmic reticulum through the ryanodine-sensitive channels. However, the ECC in lamprey muscle displays some important differences in the units of electromechanical coupling, which precede the calcium release from sarcoplasmic reticulum. The maximum contraction force in frog muscle develops during caffeine-induced contracture, which indicates that all Ca2+ stored in sarcoplasmic reticulum is released through ryanodine-sensitive channels. In contrast, in lamprey muscle, the maximum force develops not in response to high caffeine concentration, but in response to repetitive electrical stimulation. Hence, in addition to stores liberated by ryanodine-sensitive channels, some other sources of calcium ions should exist, which contribute to the contraction activation. A source of this additional Ca2+ ions can be external medium, because acetylcholine contracture is abolished in a calcium-free medium. In frog muscle, the acetylcholine contracture was abolished in a Na(+)-free solution. It was concluded that in frog muscle ECC can be triggered by changes in the transmembrane potential (depolarization-induced calcium release), while in lamprey muscle the entry of calcium ions into myoplasm as the trigger in ECC (calcium-induced calcium release). The lamprey muscle was found to be more resistant to tetrodotoxin and tetracaine, which is indicative of a role in the activation of contraction of tetrodotoxin-resistant Na+ and/or Ca2+ channels. It was concluded, that ECC mechanism in striated muscles of low vertebrates is not limited by the generally accepted scheme of depolarization-induced calcium release but can include some other schemes, which require the Ca2+ influx into the cell.

Anesthetics, Local↗
PubMed1991

Effect of low extracellular calcium and ryanodine on muscle contraction of the mouse during postnatal development.

We have examined the effects of low Ca2+ solutions, Co2+, and ryanodine on the isometric tension and contraction speed of isolated, developing mouse EDL muscles. Twitch responses of young muscles (7-14 days postnatal) were more sensitive to lowered [Ca2+]o than those of more fully developed muscles (22-35 days postnatal). Responses of EDL muscles from a middle-aged group (15-21 days postnatal) were intermediate between the two other groups. Overall, the time course of contraction in a single twitch was accelerated by low [Ca2+]o. Ca(2+)-free solution induced a 7.95 and 9.25 mV depolarization in young and "old" muscle fibres, respectively. The presence of cobalt ions (5 mM) in the Krebs solution had a similar effect as Ca(2+)-free Krebs in terms of reduction of the isometric twitch and tetanic tensions of EDL muscles from the various age groups. In contrast, the shortening of the contraction time seen with Ca(2+)-free solution did not take place following exposure to Co(2+)-containing solutions. Finally, young (7-14 days postnatal) muscles were less sensitive to the inhibitory action of ryanodine on the twitch compared with more fully developed muscles (22-35 days postnatal). Taken together, our results indicate that from birth to maturity, there is a gradual change in the spectrum of calcium utilization for the contractile process.

Animals↗
PubMed1984

Tension maintenance, calcium content and energy production of the taenia of the guinea-pig caecum under hypoxia.

When potassium (45.4 mM) was applied to isolated taenia of guinea-pig caecum, the muscle developed a rapid phasic and sustained tonic tension during aerobic conditions bubbled with 95% O2:5% CO2. Under hypoxic conditions bubbled with 95% N2:5% CO2, the taenia lost its ability to respond to high potassium with sustained tonic contraction, although it still showed rapid phasic contraction. Raising the glucose concentration from 5.5 to 55.5 mM in the presence of high potassium during hypoxia caused development of a sustained contraction which was 50% that of the muscle in aerobic conditions. In the presence of high potassium, the ATP content of the taenia decreased in hypoxia, but increased with increasing glucose concentration. When the taenia was exposed to hypoxic conditions, the amount of lactate released from the muscle increased. Raising the glucose concentration caused a further increase in lactate release in the presence of high potassium under hypoxia. Good correlations (gamma greater than 0.9) were observed between tension development, the ATP content and lactate release of the taenia in the presence of high potassium under hypoxia when the glucose concentration was varied between 5.5 and 55.5 mM. The total calcium content was increased by the presence of high potassium under aerobic conditions and the increase was abolished when the muscle was exposed to hypoxic conditions. Under hypoxia the total calcium content was not increased by raising the glucose concentration in the presence of high potassium. The cellular calcium content of the taenia, determined by the lanthanum method, was increased in the presence of high potassium under aerobic and hypoxic conditions, but the content was smaller in hypoxic conditions than in aerobic conditions. Under hypoxic conditions, raising the glucose concentration in the presence of high potassium did not affect the cellular calcium content. These results suggest that under hypoxic conditions the potassium-induced sustained contraction of the taenia is increased by raising the glucose concentration owing to increased ATP production through the glycolytic pathway, but not through mechanisms increasing the intracellular Ca concentration.

Adenosine Triphosphate↗
PubMed1986

Embryonic differentiation of fibre types in normal, paralysed and aneural avian superior oblique muscle.

The influence of innervation on the initial differentiation of muscle fibre types was investigated by using the trochlear nucleus-superior oblique muscle system of duck. The adult muscle is composed of three types of fibres (designated as type I, II, III) as identified with the histochemical techniques for ATPase pH sensitivity. Type I fibre ATPase activity was acid-stable, alkali-labile; type II alkali-stable, acid-labile; and type III both acid- and alkali-stable. These types showed variable mitochondrial alpha-glycerophosphatase dehydrogenase, nicotinamide adenine dinucleotide tetrazolium reductase, and phosphorylase activity. Type I and II fibres are primarily located in the portion of the muscle adjacent to the orbit whereas the rest of the muscle is primarily composed of type III fibres. In the normally developing muscle, type II and III fibres are present as early as embryonic day 9; one day prior to the arrival of nerve fibres in the muscle. Type I fibres are first observed on embryonic day 17. On day 22 the percentages of type I, II and III fibres are 29, 53 and 18, respectively. As the development progressed the percentages of type I and II fibres decrease and after hatching 76% of the fibres belong to type III, 17% of type II and only 7% to type I. In embryos paralysed with daily application of 3 mg d-tubocurarine (d-TC) from day 9 onwards the differentiation of type II and III fibres occurs, but type I fibres were never observed in the paralysed muscles. These muscles also contained significantly fewer myotubes than the normal muscle. By contrast, when the muscle was made aneural by permanent destruction of motor neurones on embryonic day 7 all three types of fibres differentiated. When embryos with aneural muscles were also subjected to d-TC treatment the type I fibres failed to differentiate. It is concluded that the initial differentiation of fibre types is independent of innervation and that primary myotubes are capable of differentiating into all three types of fibres. The absence of type I fibres in curarized muscles may be due to some unique effect of d-TC on the muscle itself.

Adenosine Triphosphatases↗
PubMed1995

TEM ultrastructure of the tegumental layer of Gymnophalloides seoi (Digenea: Gymnophallidae).

A transmission electron microscopic study was performed on the ultrastructure of the tegumental layer of Gymnophalloides seoi (Digenea: Gymnophallidae) metacercariae and adults. The metacercariae were obtained from naturally infected oysters, Crassostrea gigas, and the adults from experimentally infected C3H mice. The tegumental layer generally revealed a small number of foldings, numerous small vacuoles, sines, and muscle bundles. Beneath the muscle layer, nuclei of the tegumental cells were located. There was little difference in the structure of the tegument between the metacercariae and adults. The oral sucker, having well-developed muscle layers, showed a similar structure to the ventral sucker except numerous foldings in the ventral sucker. The ventral pit was surrounded by a thin syncytial layer, where a number of microtubules and mitochondria were seen. Around the ventral pit located well-developed circular and longitudinal muscles. The results showed that the ultrastructure of the tegumental layer of G. seoi metacercariae and adults revealed little difference from other trematodes in general. The ventral pit, a peculiar structure of this trematode, seems to function as a sphincter or an accessory adhesive organ.

Animals↗
PubMed1985

Dynamics of physiological changes in bovine myofibers during growth and sexual development.

Semitendinosus (ST) muscle samples were excised from 8 intact and 8 castrate male animals (Bos taurus) when they reached age end-points of 8, 12, 16, and 20 months. All three principal myofiber phenotypes (IC, IIA, IIB) increased in size with increasing age, with the IIA (fast-white) fibers usually larger than the other two types. Only at 16 and 20 months were the type II myofibers from intact males consistently larger than that from castrates. The amount of IIA fibers always exceeded that of the other two phenotypes at every age. Myofiber characteristics were more highly correlated with animal age than with either total body weight or total muscle mass. An ontogenetic scheme is proposed to illustrate the dynamic interrelationships of the three ST myofiber phenotypes.

Age Factors↗
PubMed2006

Stapedius muscle fiber characterization during postnatal development in the rat.

The stapedius muscle (SM) is reported to prevent cochlear damage by noise. Functional demands are then the ability of fast contraction with long endurance. At the end of the third postnatal week, the middle ear of the rat is completely pneumatized and according to electrophysiological data, the auditory function starts to match the adult. We investigated the developmental changes in myosin composition of SM fibres using consecutive complete SM cross-sections (taken from rats on post natal day (PND) 7, 14, 16, 21, 28, 42 and 84) which were processed by enzymehistochemistry to determine acid/alkali lability of myofibrillar adenosine triphosphatase (mATPase) and by immunohistochemistry using myosin heavy chain (MHC) antibodies (mAb). Fibres were assigned to mATPase type I, IIA, IIB, IIX or 'Miscellaneous' categories. Per mATPase category, the fibres were attributed to groups with specific MHC isoform compositions. Neonatal MHC expression could not be documented with the mAb used. However, embryonal (Emb) MHC was expressed at PND 7, very little at PND 14; at later PND fibres did not show Emb MHC. In general, the mATPase-based classification did not show large alterations after PND 21. Expression of MHC IIB, which was present in almost 50% of the fibres at PND 7 and 14, diminished to 3% at PND 84. A decrease in number of fibres expressing more than one MHC isoform was found. These results show that the SM is a precociously developing muscle compared to limb muscles and even to the diaphragm. Moreover, it is shown that the expression of the adult MHC isoform phenotype coincides with the onset of auditory function in the third postnatal week.

Adenosine Triphosphatases↗
PubMed2005

Na+-K+ pump stimulation improves contractility in damaged muscle fibers.

Skeletal muscles have a high content of Na+-K+-ATPase, an enzyme that is identical to the Na+-K+ pump, a transport system mediating active extrusion of Na+ from the cells and accumulation of K+ in the cells. The major function of the Na+-K+ pumps is to maintain the concentration gradients for Na+ and K+ across the plasma membrane. This generates the resting membrane potential, allowing the propagation of action potentials, excitation-contraction coupling and force development. Muscles exposed to (1) high extracellular K+ or (2) low extracellular Na+ show a considerable loss of force. A similar force decline is elicited by (3) increasing Na+ permeability or (4) decreasing K+ permeability. Under all of these four conditions, stimulation of the Na+-K+ pumps can restore contractility. Following exposure to electroporation or fatiguing stimulation, muscle cell membranes develop leaks to Na+ and K+ and a partially reversible loss of force. The restoration of force is abolished by blocking the Na+-K+ pumps and markedly improved by stimulating the Na+-K+ pumps with beta 2-agonists, calcitonin gene-related peptide, or dbcAMP. These observations indicate that the Na+-K+ pumps are important for the functional compensation of the commonly occurring loss of muscle cell integrity. Stimulation of the Na+-K+ pumps with beta 2-agonists or other agents may be of therapeutic value in the treatment of muscle cell damage induced by electrical shocks, prolonged exercise, burns, or bruises.

Cell Membrane↗
PubMed1992

Evaluation of DNA flow cytometry as a screening test for bladder cancer.

At this present time, we feel that there is no role for DNA flow cytometry (FCM), or indeed DNA studies by any other method, to be used as a screening procedure for patients with no prior history of bladder cancer due to the high false-positive rate found when monitoring exfoliated urothelial cells. On the other hand, for patients who have had a superficial transitional cell carcinoma (TCC), which has a documented 50% recurrence rate, and depending on pathological features, a progression rate from 7 to 45%, DNA FCM provides a sensitive method to predict future disease recurrence. It provides an extremely effective way to predict future progression and further acts as a method to monitor changes in the malignant potential of the patient's disease. For those patients with a past history of superficial TCC who develop abnormal ploidy without any overt tumor, 80% will, within the next four years, suffer a disease recurrence. For the patient who has a Ta TCC and receives intravesical Bacillus Calmette-Guerin (BCG), the development of abnormal ploidy in bladder washing specimens is the single best indicator for future disease recurrence. Similarly, a negative DNA FCM of a bladder washing at six months after intravesical therapy is an excellent predictor of no further occurrence. In patients with superficial TCC, ploidy of the initial and recurrent tumor predicts for future progression. Half of those patients with stage Ta bladder cancer with two successive aneuploid bladder tumors develop muscle invasive disease within one year, while three-fourths develop advanced disease within two years after recurrence of their second aneuploid lesion.(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinoma, Transitional Cell↗
PubMed1992

Isolation and characterization of macrophages from rat embryonic muscle culture.

We have previously described the wide distribution of resident macrophages in normal rat skeletal muscle. In this study, we investigated the characteristics of the macrophages that occur in rat embryo muscle cultures. We showed that cells of monocyte-macrophage lineage are present in primary muscle cultures of rat embryos (18 days in gestation) and that these cells form morphologically and phenotypically heterogeneous populations, based on their reaction with monoclonal antibodies ED1, ED2, ED3, and OX43. Constitutively Ia+ cells with dendritic appearance were also observed. Furthermore, we established the procedure for isolation of macrophages from the primary muscle cultures. The isolated cells, mostly ED1+, expressed class I and CD4 antigens and bore complement (C3) receptors on their surfaces. The fact that cell of monocyte-macrophage lineage occur in the embryonic muscle suggests that during embryogenesis these cells may enter the developing muscle and give rise to a population of tissue-associated macrophages.

Animals↗
PubMed1992

MPTP induced hemiparkinsonism in monkeys: behavioral, mechanographic, electromyographic and immunohistochemical studies.

A single infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine (MPTP) into the right internal carotid artery of Macaca mulatta monkeys resulted in akinesia and rigidity of the contralateral limb. The immunohistochemical study revealed a dramatic reduction in the number of TH-immunoreactive cells in the substantia nigra of the infused side (70-81%). After unilateral MPTP-treatment movement parameters and EMG activity were altered; the agonist muscle developed increased EMG activity associated with a shift of antagonist muscle activity. These results confirm that hemiparkinsonian monkeys are a valuable model of parkinsonism which can be useful in studies of movement disorder physiology and therapy of Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗