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PubMed1998

Bradykinin and muscle stretch alter contralateral cat neck muscle spindle output.

The objective of this study was to investigate the activity of primary and secondary muscle spindle afferents (MSAs) in neck muscles, when the contralateral splenius or trapezius muscles were (1) exposed to i.m. injection of bradykinin (BK) (6-86 microg/ml), (2) stretched, (3) stretched during exposure to BK or (4) stretched after exposure to BK. It was found that injection of BK, muscle stretch and the combination of the two stimuli significantly excited primary and secondary MSAs via reflex effects onto static fusimotor neurones. BK, alone, and in combination with muscle stretch, induced more frequent, potent and long lasting effects as compared to muscle stretch. The effects of muscle stretch was significantly increased after exposure of BK, indicating that stretch-sensitive nerve-endings within neck muscles are sensitised by BK. The results are discussed in relation to the disturbances in motor co-ordination and proprioception found in patients suffering from chronic muscle pain in the cervical region.

Animals↗

PubMed1998

Muscle spindles are concentrated in the superior vocalis subcompartment of the human thyroarytenoid muscle.

It is hypothesized that different parts of the thyroarytenoid muscle (TA) are functionally specialized. Specifically, the TA is divided into a lateral muscularis compartment and a medial vocalis compartment. This study examined the distribution of muscle spindles throughout the human TA as an indicator of these functional differences. Histological cross-sections from the anterior, middle, and posterior regions of five human membranous vocal folds were examined for the number and location of muscle spindles. There was an average of 6.1 muscle spindles in sections from each region with no significant variation between the different regions (p < .05). However, in sections from all three regions, the muscle spindles were always found to be concentrated in the superior medial quadrant of the TA (mean 85.9%, p < .01). The inferior medial, superior lateral, and inferior lateral quadrants of the TA contained 11.96%, 2.17%, and 0%, respectively, of the total muscle spindles. Within the superior medial quadrant, most of the muscle spindles were localized in the most superficial part of the muscle. The results of this study demonstrate that the majority of TA muscle spindles are concentrated in its superior medial quadrant, an area we have termed the superior vocalis subcompartment (SC). This finding suggests that the superior vocalis SC is functionally distinct from the remainder of the TA. It is hypothesized that tension in the superior vocalis SC can be controlled independently from the remainder of the TA, and this capability is used to effect the biomechanics of vocal fold vibration during phonation.

Humans↗

PubMed1998

Acute and sustained effects of isometric and lengthening muscle contractions on high-energy phosphates and glycogen metabolism in rat tibialis anterior muscle.

Previous studies have shown that lengthening contractions, in contrast to isometric contractions, readily result in sustained malfunctioning of the exercised muscles. The present study was performed to investigate whether an exercise period with many (240) lengthening contractions (LC) results in alterations in muscle high-energy phosphates and inosine monophosphate (IMP) content, different from muscles performing a few (60) lengthening or a few (60) or many (240) isometric contractions (IC). Moreover, we sought for a possible cause(s) of the inability to replenish muscle glycogen stores following LC. Rat tibialis anterior muscles were subjected in vivo to either 60 or 240 LC or IC. Structural muscle damage occurred only after 240 LC. The fact that tissue glycogen levels declined to a similar extent during LC and IC suggests that the energy demand was comparable during both types of exercise. Nevertheless, the observation that on the one hand tissue stores of adenine nucleotides showed a greater decline, and on the other hand the tissue content of IMP increased to a significantly higher level after LC than after IC, clearly indicates that muscle energy metabolism is more disturbed during LC than during IC. The high tissue levels of IMP may contribute to impaired mechanical function as previously observed in muscles subjected to LC. In contrast to 240 IC, 24 hours after 240 LC, tissue glycogen stores and high-energy phosphate levels were not restored to control values. The present findings indicate that depressed glycogen synthase activity and impaired activity of the mitochondrial marker enzyme cytochrome C oxidase probably contribute to a continuous disturbance of energy metabolism in the exercised muscles during the 24 hours following 240 LC.

Adenosine Diphosphate↗

PubMed1986

EMG recording in human lip muscles: can single muscles be isolated?

Electromyography, recording the electrical activity of muscles, is an electrophysiological method that has been used widely in the study of movement performance by human subjects. Borrowing from the tradition of electromyographic studies of limb muscles, investigators interested in speech production have used the method to address many important experimental questions. Unfortunately, data recorded from craniofacial muscles generally have been discussed without reference to problems of interpretation that could arise due to the unique anatomical features of the muscles, particularly the lip muscles. Anatomical data show that the fibers of different muscles of the lips are interdigitated so that fibers with differing spatial orientation typically are found within a small section of lower lip tissue. The anatomical data are consistent with results of physiological studies of the lower lip muscles that have suggested that motor units with different physiological characteristics are found within a single recording site. Together, the anatomical and electrophysiological data suggest that, even with intramuscular electrodes, the probability of recording from a single muscle of the lip in isolation is extremely low. The fact that the activity of more than one muscle is likely to be sampled critically determines the nature of the conclusions that can be drawn from the data.

Electromyography↗

PubMed1999

Age-related changes and location of type I, III, IV, V and VI collagens during development of four foetal skeletal muscles of double-muscled and normal bovine animals.

The aim of this work was to study the variability in the quantities of hydroxyproline, of type I and III collagens and in the location of types, I, III, IV, V, VI in four muscles of normal and double-muscled (DM) cattle. Samples were collected from foetuses at different ages post-conception. Both in the two genetic types and in muscles, from 110 days, types I, III, V, VI were located in perymisium and types I, IV, V, VI in endomysium. The amounts of hydroxyproline and of type I collagen increased from 150 to 180 or 230 days then decreased up to 260 days, with a trend to lower quantities in muscles of DM animals. Depending on the muscle and of the genetic type, amounts of type III, or changed as those of type I, or remained stable. Whatever the genetic type, at the end of gestation, proportions of type I and III in the total collagen are not identical in the four muscles, differences between muscles being particularly marked for type III, CT and MA muscles being the richer in this type. In addition, these two muscles contained less type III in DM animals than in normal ones.

Aging↗

PubMed1995

Effects of strength training on muscle hypertrophy and muscle cell disruption in older men.

To determine whether a total body, heavy resistance, strength training (ST) program can significantly increase muscle strength and hypertrophy without muscle cell disruption and soreness in older men, 35 sedentary male subjects between the ages of 50 and 69 years of age (60 +/- 5, mean +/- SD) were studied. Twelve served as inactive controls. Muscular strength, cross-sectional muscle area, serum creatine kinase (CK) activity and perceived soreness were assessed before and after a 16 wk heavy resistance ST program. The ST program resulted in a 43% increase in muscular strength (p < 0.001), and a 7.2% increase in midthigh muscle area (153 +/- 24 vs 164 +/- 23 cm2, p < 0.001). There were no significant changes in strength or muscle area in the inactive control group. Peak serum CK levels were approximately twofold above baseline (278 +/- 175 vs 133 +/- 88 U/l, p < 0.01) 8 h after the first regular training session. At the end of training, the peak rise in CK levels was also reached 8 h after exercise, but was reduced substantially at the same absolute (p < 0.01) and relative resistance loads (p < 0.01) compared to the first training session. Muscle soreness after exercise was only occasionally reported at the beginning of training and was almost nonexistent after training. These results indicate that middle-aged and older men can safely participate in a total body strength training program, intense enough to produce substantial increases in muscle strength and hypertrophy, without promoting muscle soreness or significant muscle cell disruption.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

PubMed1996

Myocyte-specific enhancer factor 2 acts cooperatively with a muscle activator region to regulate Drosophila tropomyosin gene muscle expression.

MEF2 (myocyte-specific enhancer factor 2) is a MADS box transcription factor that is thought to be a key regulator of myogenesis in vertebrates. Mutations in the Drosophila homologue of the mef2 gene indicate that it plays a key role in regulating myogenesis in Drosophila. We show here that the Drosophila tropomyosin I (TmI) gene is a target gene for mef2 regulation. The TmI gene contains a proximal and a distal muscle enhancer within the first intron of the gene. We show that both enhancers contain a MEF2 binding site and that a mutation in the MEF2 binding site of either enhancer significantly reduces reporter gene expression in embryonic, larval, and adult somatic body wall muscles of transgenic flies. We also show that a high level of proximal enhancer-directed reporter gene expression in somatic muscles requires the cooperative activity of MEF2 and a cis-acting muscle activator region located within the enhancer. Thus, mef2 null mutant embryos show a significant reduction but not an elimination of TmI expression in the body wall myoblasts and muscle fibers that are present. Surprisingly, there is little effect in these mutants on TmI expression in developing visceral muscles and dorsal vessel (heart), despite the fact that MEF2 is expressed in these muscles in wild-type embryos, indicating that TmI expression is regulated differently in these muscles. Taken together, our results show that mef2 is a positive regulator of tropomyosin gene transcription that is necessary but not sufficient for high level expression in somatic muscle of the embryo, larva, and adult.

Animals↗

PubMed1996

Distinct troponin T genes are expressed in embryonic/larval tail striated muscle and adult body wall smooth muscle of ascidian.

During development of the ascidian Halocynthia roretzi, the tadpole larva hatched from the tailbud embryo metamorphoses to the sessile adult with a body wall muscle. Although the adult body wall muscle is morphologically nonsarcomeric smooth muscle, it contains troponin complex consisting of three subunits (T, I, and C) as do vertebrate striated muscles. Different from vertebrate troponins, however, the smooth muscle troponin promotes actomyosin Mg2+-ATPase activity in the presence of high concentration of Ca2+, and this promoting property is attributable to troponin T. To address whether the embryonic/larval tail striated muscle and the adult smooth muscle utilize identical or different regulatory machinery, we cloned troponin T cDNAs from each cDNA library. The embryonic and the adult troponin Ts were encoded by distinct genes and shared only <60% identity with each other. Northern blotting and whole mount in situ hybridization revealed that these isoforms were specifically expressed in the embryonic/larval tail striated muscle and the adult smooth muscle, respectively. These results may imply that these isoforms regulate actin-myosin interaction in different manners. The adult troponin T under forced expression in mouse fibroblasts was unexpectedly located in the nuclei. However, a truncated protein with a deletion including a cluster of basic amino acids colocalized with tropomyosin on actin filaments. Thus, complex formation with troponin I and C immediately after the synthesis is likely to be essential for the protein to properly localize on the thin filaments.

Actomyosin↗

PubMed1998

MEF2B is a component of a smooth muscle-specific complex that binds an A/T-rich element important for smooth muscle myosin heavy chain gene expression.

To understand smooth muscle-specific gene expression, we have focused our studies on the smooth muscle myosin heavy chain (SMHC) gene, a smooth muscle-specific marker. In this study, we demonstrate that the SMHC promoter region (-1594 to -1462 base pairs) containing the A/T-rich element can activate the heterologous thymidine kinase promoter in smooth muscle cells, but not in fibroblasts. Mutations of this A/T-rich element decreased SMHC promoter activity significantly. Both gel mobility shift assays and DNase I footprinting revealed that this region binds to specific protein complexes from smooth muscle nuclear extracts, whereas nuclear extracts from skeletal muscle and fibroblasts produced a different binding pattern. We also demonstrate that the protein complex obtained from smooth muscle nuclear extract reacts with MEF2B-specific antibody, but not with antibodies specific to MEF2A, MEF2C, or MEF2D, suggesting that only MEF2B protein binds to the A/T-rich element. Furthermore, MEF2B overexpression in smooth muscle cells up-regulated the SMHC promoter, suggesting that MEF2B is important for SMHC gene regulation. This is the first report demonstrating a role for MEF2 factors in smooth muscle-specific gene expression.

3T3 Cells↗

PubMed2000

Expression of gamma -sarcoglycan in smooth muscle and its interaction with the smooth muscle sarcoglycan-sarcospan complex.

The sarcoglycan complex in striated muscle is a heterotetrameric unit integrally associated with sarcospan in the dystrophin-glycoprotein complex. The sarcoglycans, alpha, beta, gamma, and delta, are mutually dependent with regard to their localization at the sarcolemma, and mutations in any of the sarcoglycan genes lead to limb-girdle muscular dystrophies type 2C-2F. In smooth muscle beta- and delta-sarcoglycans are associated with epsilon-sarcoglycan, a glycoprotein homologous to alpha-sarcoglycan. Here, we demonstrate that gamma-sarcoglycan is also a component of the sarcoglycan complex in the smooth muscle. First, we show the presence of gamma-sarcoglycan in a number of smooth muscle-containing organs, and we verify the existence of identical transcripts in skeletal and smooth muscle. The specificity of the expression of gamma-sarcoglycan in smooth muscle was confirmed by analysis of smooth muscle cells in culture. Next, we provide evidence for the association of gamma-sarcoglycan with the sarcoglycan-sarcospan complex by biochemical analysis and comparison among animal models for muscular dystrophy. Moreover, we find disruption of the sarcoglycan complex in the vascular smooth muscle of a patient with gamma-sarcoglycanopathy. Taken together, our results prove that the sarcoglycan complex in vascular and visceral smooth muscle consists of epsilon-, beta-, gamma-, and delta-sarcoglycans and is associated with sarcospan.

Amino Acid Sequence↗

PubMed2001

A novel role of neuregulin in skeletal muscle. Neuregulin stimulates glucose uptake, glucose transporter translocation, and transporter expression in muscle cells.

Neuregulins regulate the expression of acetylcholine receptor genes and induce development of the neuromuscular junction in muscle. In studying whether neuregulins regulate glucose uptake in muscle, we analyzed the effect of a recombinant neuregulin, (r)heregulin-beta1-(177-244) (HRG), on L6E9 muscle cells, which express the neuregulin receptors ErbB2 and ErbB3. L6E9 responded acutely to HRG by a time- and concentration-dependent stimulation of 2-deoxyglucose uptake. HRG-induced stimulation of glucose transport was additive to the effect of insulin. The acute stimulation of the glucose transport induced by HRG was a consequence of the translocation of GLUT4, GLUT1, and GLUT3 glucose carriers to the cell surface. The effect of HRG on glucose transport was dependent on phosphatidylinositol 3-kinase activity. HRG also stimulated glucose transport in the incubated soleus muscle and was additive to the effect of insulin. Chronic exposure of L6E9 cells to HRG potentiated myogenic differentiation, and under these conditions, glucose transport was also stimulated. The activation of glucose transport after chronic HRG exposure was due to enhanced cell content of GLUT1 and GLUT3 and to increased abundance of these carriers at the plasma membrane. However, under these conditions, GLUT4 expression was markedly down-regulated. Muscle denervation is associated with GLUT1 induction and GLUT4 repression. In this connection, muscle denervation caused a marked increase in the content of ErbB2 and ErbB3 receptors, which occurred in the absence of alterations in neuregulin mRNA levels. This fact suggests that neuregulins regulate glucose transporter expression in denervated muscle. We conclude that neuregulins regulate glucose uptake in L6E9 muscle cells by mechanisms involving the recruitment of glucose transporters to the cell surface and modulation of their expression. Neuregulins may also participate in the adaptations in glucose transport that take place in the muscle fiber after denervation.

Animals↗

PubMed1989

Expression of nuclear lamin A and muscle-specific proteins in differentiating muscle cells in ovo and in vitro.

Primary cultures and tissue samples of chicken embryonic muscle were immunologically probed for the expression of muscle-specific proteins, such as myosin heavy chain and the tropomyosins, as well as for the nuclear lamina protein, lamin A. As determined by quantitative immunoblotting, the expression of lamin A and the muscle-specific proteins were at low levels or absent in predifferentiation myoblasts both in vitro and in ovo. During differentiation, an increase of lamin A expression preceded the induction to high levels of expression of muscle-specific proteins. Immunofluorescence staining of chicken embryonic muscle cells in culture also indicates an accumulation of lamin A before the induction of muscle-specific proteins expression. Furthermore, the accumulation of lamin A reached a plateau before the muscle-specific proteins during muscle development. In two dimensional NEPHGE gel analysis of immunoprecipitated lamin A, no detectable change in the ratio of the acidic/basic isoelectric variants of lamin A was observed during myogenesis. A potential role for lamin A in the mechanisms which underlie the differential and coordinate expression of muscle-specific genes is proposed.

Animals↗

PubMed2000

Novel immunolocalization of alpha-synuclein in human muscle of inclusion-body myositis, regenerating and necrotic muscle fibers, and at neuromuscular junctions.

Alpha-synuclein (alpha-syn) is an important component of neuronal and glial inclusions in brains of patients with several neurodegenerative disorders. Sporadic inclusion-body myositis (s-IBM) is the most common progressive muscle disease of older patients. Its muscle phenotype shows several similarities with Alzheimer disease brain. A distinct feature of s-IBM pathology is specific vacuolar degeneration of muscle fibers characterized by intracellular amyloid inclusions formed by both amyloid-beta (Abeta) and paired-helical filaments composed of phosphorylated tau. We immunostained alpha-syn in muscle biopsies of s-IBM, disease-control, and normal patients. Approximately 60% of Abeta-positive vacuolated muscle fibers (VMF) contained well-defined inclusions immunoreactive with antibodies against alpha-syn. In those fibers. alpha-syn co-localized with Abeta, both by light microscopy, and ultrastructurally. Paired-helical filaments did not contain alpha-syn immunoreactivity. In all muscle biopsies, alpha-syn was strongly immunoreactive at the postsynaptic region of the neuromuscular junctions. alpha-syn immunoreactivity also occurred diffusely in regenerating and necrotic muscle fibers. In cultured human muscle fibers, alpha-syn and its mRNA were expressed by immunocytochemistry, immunoblots, and Northern blots. Our study provides the first demonstration that alpha-syn participates in normal and pathologic processes of human muscle. Therefore. its function is not exclusive to the brain and neurodegenerative diseases.

Cells, Cultured↗

PubMed1993

Muscle hypertrophy experimentally induced by administration of denervated muscle extract.

The effects of systemic administration of muscle extract on normal muscle were studied. Male Wistar rats received intraperitoneal injections of normal and denervated muscle extract over 5 consecutive days. Soleus muscles were then submitted to histological, histochemical and quantitative-morphometric analysis. The group receiving denervated muscle extract showed considerable muscle fiber hypertrophy, together with the formation of new fibers suggestive of hyperplasia. The systemic administration of denervated muscle extract was shown to have a considerable myotrophic effect on normal muscle, evident in the hypertrophy and hyperplasia of muscle fibers.

Animals↗

PubMed2000

Skeletal muscle reinnervation by reduced axonal numbers results in whole muscle force deficits.

Patients sustaining a peripheral nerve injury will frequently experience residual muscle weakness after muscle reinnervation, even if the nerve repair is performed under optimal circumstances to allow rapid muscle reinnervation. The mechanisms responsible for this contractile dysfunction remain unclear. It is hypothesized that after peripheral nerve injury and repair, a reduced number of axons are available for skeletal muscle reinnervation that results in whole muscle force and specific force deficits. A rat model of peroneal nerve injury and repair was designed so that the number of axons available for reinnervation could be systematically reduced. In adult rats, the peroneal nerve to the extensor digitorum longus muscle was either left intact (sham group, n = 8) or divided and repaired with either 50 percent (R50 group, n = 7) or 100 percent (R100 group, n = 8) of the axons in the proximal stump included in the repair. Four months after surgery, maximal tetanic isometric force was measured and specific force was calculated for each animal. Mean tetanic isometric force for extensor digitorum longus muscles from R50 rats (2765.7 +/- 767.6 mN) was significantly lower than sham (4082.8 +/- 196.5 mN) and R100 (3729.0 +/-370.2 mN) rats (p < 0.003). Mean specific force calculations revealed significant deficits in both the R100 (242.1 +/- 30 kN/m2) and R50 (190.6 +/- 51.8 kN/m2) rats compared with the sham animals (295.9 +/- 14 kN/m2) (p < 0.0005). These data support our hypothesis that after peripheral nerve injury and repair, reinnervation of skeletal muscle by a reduced number of axons results in a reduction in tetanic isometric force and specific force. The greater relative reduction in specific force compared with absolute force production after partial nerve repair may indicate that a population of residual denervated muscle fibers is responsible for this deficit.

Animals↗

PubMed1985

Organization of skeletal muscle in the urodele Triturus cristatus: muscle fibre types and motor units.

Four muscle fibre types are described in the biceps and extensor digitorum communis muscles of the newt forelimb. The histological criteria forming the basis for the distinctions include differential staining with p-phenylenediamine and succinate dehydrogenase histochemistry and electron microscopy. In addition, three distinctive motor unit types are described for the biceps muscle. These are fast units, slow units and intermediate units. The structure of muscle fibre and the physiological characteristics of muscle fibres belonging to each motor unit, have been correlated by using iontophoretic passage of Lucifer yellow into muscle fibres belonging to physiologically characterized motor units and their subsequent histological identification by the succinate dehydrogenase reaction. The three motor unit types correspond to slow muscle fibres, intermediate muscle fibres and two classes of fast muscle fibres.

Aminopyridines↗

PubMed1993

Afferent signals from pigeon extraocular muscles modify the activity of neck muscles during the vestibulocollic reflex.

Movements of the head and eye which, together, result in changes in the direction of gaze are linked in a number of species, including man, and eye position is known to affect the activity of neck muscles. This head-eye linkage has generally been ascribed to modification of neck muscle activity by internal estimates of eye position derived from motor commands. We have recently shown that afferent signals from stretch receptors in the extraocular muscles are involved in the moment-to-moment control of eye movements during the vestibuloocular reflex (VOR). We have now studied the interactions between head and eye movements by recording the electromyographic activity of several neck muscles during horizontal (yaw) or frontal (roll tilt) vestibular stimulation. Such a stimulus evokes a VOR in the eyes and a vestibulocollic reflex (VCR) in neck muscles. Imposing movements on one eye at saccadic velocities produced considerable inhibition of the VCR response of a number of neck muscles. The magnitude of these effects was dependent on the parameters of the imposed eye movement. Thus systematic changes were seen when the amplitude, velocity or direction of eye movement was varied. Movement of the eye in the opposite direction to that produced by a normal VOR produced a large inhibition of the VCR response, whereas movements in the same direction as the VOR produced only modest inhibition of the VCR response of the neck muscles tested. Slow, sinusoidal, imposed eye movements that mimicked the slow phase of the VOR produced changes in the gain of the VCR response which appear to correct for errors in the imposed eye velocity and thus tend to maintain the direction of gaze. The results show that changes in eye position have striking effects on the electromyographic activity of neck muscles during the VCR, and strongly suggest that extraocular muscle afferent signals are involved in head-eye coordination.

Afferent Pathways↗

PubMed2004

Influence of masticatory muscle pain on electromyographic activities of cervical muscles in patients with myogenous temporomandibular disorders.

The present study tested the hypothesis that the resting electromyographic (EMG) activities of sternocleidomastoid and trapezius muscles of myogenous temporomandibular disorder (TMD) patients would be significantly greater than healthy individuals. Eight masticatory muscle pain patients without disc interference disorders (DID) and 30 patients with DID along with 41 matched control subjects were included in the study. The resting EMG activities of sternocleidomastoid and trapezius muscles were recorded with a portable EMG machine. Pain intensities described over the muscles were recorded with a 100 mm visual analogue scale. The two groups of patients had significantly higher resting activities compared with control subjects. Patients (in both groups) who had pain in sternocleidomastoid and trapezius muscles reported significantly higher resting activities in the respective muscles than patients who were free of pain and the controls. The presence of pain over the examined muscles showed significant association with the myogenous TMDs without DID. The observed association of the cervical muscles with myogenous TMDs is expected to be a result of functional link between masticatory and cervical muscles. The present findings suggest that the myogenous TMDs without DID could be a distinct sub-group that can be a part of broader regional or generalized diseased entity.

Adult↗