Embryonic and postnatal development of masticatory and tongue muscles

This review summarizes findings concerning the unique developmental characteristics of mouse head muscles (mainly the masticatory and tongue muscles) and compares their characteristics with those of other muscles. The developmental origin of the masticatory muscles is the somitomeres, whereas the tongue and other muscles, such as the trunk (deep muscles of the back, body wall muscles) and limb muscles, originate from the somites. The program controlling the early stages of masticatory myogenesis, such as the specification and migration of muscle progenitor cells, is distinctly different from those in trunk and limb myogenesis. Tongue myogenesis follows a similar regulatory program to that for limb myogenesis. Myogenesis and synaptogenesis in the masticatory muscles are delayed in comparison with other muscles and are not complete even at birth, whereas the development of tongue muscles proceeds faster than those of other muscles and ends at around birth. The regulatory programs for masticatory and tongue myogenesis seem to depend on the developmental origins of the muscles, i.e., the origin being either a somite or somitomere, whereas myogenesis and synaptogenesis seem to progress to serve the functional requirements of the masticatory and tongue muscles. This study was supported by grants-in-aid for funding scientific research (nos. 13671955 and 16591871), the Bio-ventures and High-Technology Research Center of the Ministry of Education, Culture, Sports, Science, and Technology of Japan, and the Science Research Promotion Fund from the Promotion and Mutual Aid Corporation for Private Schools of Japan.     

Activities of 3-hydroxybutyrate dehydrogenase, 3-oxoacid CoA-transferase and acetoacetyl-CoA thiolase in relation to ketone-body utilisation in muscles from vertebrates and invertebrates

1. The activities of 3-hydroxybutyrate dehydrogenase were non-detectable in muscles of invertebrates and marine teleost fish; activities were found in muscles of amphibia, reptiles and mammals and also in an elasmobranch fish. Muscles were classified into three groups according to the activities of 3-oxoacid CoA-transferase: muscles with very low activities (less than 0.01 mumol x min-1 x g-1) which obtain energy for contraction from anaerobic glycolysis; muscles with low activities (greater than 0.01 less than 5 mumol x min-1 x g-1) which include insect flight muscles, muscles of other invertebrates and skeletal muscles of higher vertebrates; muscles with high activities of 3-oxoacid CoA-transferase (greater than 5 mumol x min-1 x g-1) which are characterised by continuous mechanical activity for long periods of time, e.g. heart, diaphragm, postural and some smooth muscles of mammals. 2. It is suggested that ketone bodies may be important fuels for muscles in the very low and low activity groups during starvation, when the muscle is at rest. The muscles in the high activity group may use ketone bodies when they are available in the blood to provide energy for mechanical activity. Since these muscles provide a continuous vital physiological function, they must always be provided with a fuel for respiration and, in a similar manner to brain, they may utilise either glucose or ketone bodies.     

Oro-facial muscles: internal structure,function and ageing

Structure and function are reviewed in the masticatory muscles and in the muscles of the lower face and tongue. The enormous strength of jaw closure is in large part due to the pinnated arrangement of the muscle fibres in the masseter. This muscle, like other masticatory muscles, is unusual in that the cell bodies of the muscle spindle afferents lie in the brain stem rather than in an external ganglion; spindles are absent in the lower facial muscles. Although few data are available, the numbers of motor units in the masticatory muscles, and probably in the lower facial muscles also, appear to he much greater than in limb muscles. The motor units in the facial and tongue muscles are largely composed of histochemical type II (‘fast-twitch’) fibres, but in the masticatory muscles there are substantial numbers of fibres intermediate between type I (‘slow twitch’) and type II, and fibre type grouping is present. In comparison with limb muscles, there is little information on ageing changes in oro-facial muscles. The masticatory muscles do, however, show some atrophy and loss of X-ray density, while motor unit twitches are prolonged. Strength is reduced in the tongue and masticatory muscles. It is known that limb muscle properties are largely governed by their innervation, both through the pattern and amount of impulse activity, and the delivery of trophic messengers; the situation for oro-facial muscles is unclear. The structural and functional differences between the two types of muscle indicate the need for conducting ageing studies on the oro-facial muscles, rather than relying on extrapolations from limb muscles.     

Activity in torso muscles during relaxed standing

Electromyographic activity of erector spinae, external oblique, and rectus abdominis muscles was studied during relaxed standing compared to lying down. Activity in the forearm extensors and forearm flexors was also studied. Surface electrodes were used. Each of the torso muscles exhibited 0.2 microV of activity and the forearm muscles 0.1 microV while subjects were relaxed and lying down. During quiet standing the erector spinae, external oblique, and rectus abdominis muscles showed a median activity of 1.0 microV, 2.5 microV, and 0.7 microV respectively (for a minimum of ten 10-sec samples per subject). Examination of the integrated records during standing revealed no periods without increased muscle activity in the torso muscles. By contrast, activity in the forearm muscles did not increase during standing. The major superficial muscles of posture in the torso appear to act as guy wires, being continually active during standing. There is no support for hypotheses of passive support for the torso, nor do torso muscles act in either/or fashion; both anterior and posterior muscles are active at once. There is no sign of generally increased muscle tone in all muscles or in extensors; only the postural muscles are continuously active.     

Ret signalling integrates a craniofacial muscle module during development

An appropriate organisation of muscles is crucial for their function, yet it is not known how functionally related muscles are coordinated with each other during development. In this study, we show that the development of a subset of functionally related head muscles in the zebrafish is regulated by Ret tyrosine kinase signalling. Three genes in the Ret pathway (gfra3, artemin2 and ret) are required specifically for the development of muscles attaching to the opercular bone (gill cover), but not other adjacent muscles. In animals lacking Ret or Gfra3 function, myogenic gene expression is reduced in forming opercular muscles, but not in non-opercular muscles derived from the same muscle anlagen. These animals have a normal skeleton with small or missing opercular muscles and tightly closed mouths. Myogenic defects correlate with a highly restricted expression of artn2, gfra3 and ret in mesenchymal cells in and around the forming opercular muscles. ret(+) cells become restricted to the forming opercular muscles and a loss of Ret signalling results in reductions of only these, but not adjacent, muscles, revealing a specific role of Ret in a subset of head muscles. We propose that Ret signalling regulates myogenesis in head muscles in a modular manner and that this is achieved by restricting Ret function to a subset of muscle precursors.     

Long-term activity in upper- and lower-limb muscles of humans.

Despite limited data on humans, previous studies suggest that there is an association between the duration of daily muscle activity and the proportion of type I muscle fibers. We quantified the activity of limb muscles in healthy men and women during normal use and compared these measurements with published reports on fiber-type proportions. Seven men (age range = 21-28 yr) and seven women (age range = 18-26 yr) participated in two 10-h recording sessions. Electromyogram (EMG) activity of four muscles in nondominant upper (first dorsal interosseus and biceps brachii) and lower limbs (vastus medialis and vastus lateralis) was recorded with surface electrodes. Hand and arm muscles were active for 18% of the recording time, whereas leg muscles were active for only 10% of the recording time. On average, upper-limb muscles were activated 67% more often than lower-limb muscles. When lower-limb muscles were activated, however, the mean amplitude of each burst was greater in leg muscles [18 and 17% maximum voluntary contraction (MVC)] compared with hand (8% MVC) and arm (6% MVC) muscles. Temporal association in activity between pairs of muscles was high for the two lower-limb muscles (r2 = 0.7) and relatively weak for the two upper-limb muscles (r2 = 0.09). Long-term muscle activity was only different between men and women for the biceps brachii muscle. We found no relation between duration of muscle activity in 10-h recordings and the reported values of type I fibers in men and women.     

Susceptibility to sarcomere injury induced by single stretches of maximally activated muscles of mdx mice.

The purpose was to investigate the contribution of mechanical damage to sarcomeres to the greater susceptibility of dystrophic muscle fibers to contraction-induced injury. Single stretches provide an effective method for studying mechanical factors that contribute to the initiation of contraction-induced injury. We hypothesized that, after single stretches, the deficits in isometric force would be greater for muscles of mdx than C57BL/10 mice, whereas membrane damage would be minimal for all muscles. Extensor digitorum longus (EDL) and soleus muscles of mice were removed under anesthesia with Avertin (tribromoethanol). During the plateau of a maximum isometric contraction in vitro, muscles were stretched through single strains of 20-60% fiber length. Isometric force was remeasured 1 min later, and muscles were then incubated in procion orange dye to identify fibers with membrane damage. Force deficits at 1 min were two- to threefold greater for EDL muscles of mdx compared with C57BL/10 mice, whereas no significant differences were observed between soleus muscles of mdx and C57BL/10 mice. For all muscles, membrane damage was minimal and not significantly increased by single stretches for either strain of mice. These data support a critical role of dystrophin maintaining sarcomere stability in EDL muscles, whereas soleus muscles retain abilities, in the absence of dystrophin, not different from control muscles to resist sarcomere damage.     

Development of a finite element musculoskeletal model with the ability to predict contractions of three-dimensional muscles

Representation of realistic muscle geometries is needed for systematic biomechanical simulation of musculoskeletal systems. Most of the previous musculoskeletal models are based on multibody dynamics simulation with muscles simplified as one-dimensional (1D) line-segments without accounting for the large muscle attachment areas, spatial fibre alignment within muscles and contact and wrapping between muscles and surrounding tissues. In previous musculoskeletal models with three-dimensional (3D) muscles, contractions of muscles were among the inputs rather than calculated, which hampers the predictive capability of these models. To address these issues, a finite element musculoskeletal model with the ability to predict contractions of 3D muscles was developed. Muscles with realistic 3D geometry, spatial muscle fibre alignment and muscle-muscle and muscle-bone interactions were accounted for. Active contractile stresses of the 3D muscles were determined through an efficient optimization approach based on the measured kinematics of the lower extremity and ground force during gait. This model also provided stresses and strains of muscles and contact mechanics of the muscle-muscle and muscle-bone interactions. The total contact force of the knee predicted by the model corresponded well to the in vivo measurement. Contact and wrapping between muscles and surrounding tissues were evident, demonstrating the need to consider 3D contact models of muscles. This modelling framework serves as the methodological basis for developing musculoskeletal modelling systems in finite element method incorporating 3D deformable contact models of muscles, joints, ligaments and bones.     

Power outputs of slow and fast skeletal muscles of mice

The purpose of this study was to contrast the frequency-power relationship of slow soleus and fast extensor digitorum longus (EDL) muscles to their frequency-force relationships and to investigate factors involved in the development of maximum power during a single contraction. Stimulation frequency-force and stimulation frequency-power relationships were determined for soleus and EDL muscles of the mouse for single contractions in situ at 35 degrees C. Power was measured during isovelocity shortening contractions with displacement through 10% of fiber length at the optimum velocity. Optimum velocity was defined as the shortening velocity for the generation of maximum power for a given stimulation frequency. Both force (N/cm2) and power (watts/kg) increased with stimulation frequency until a plateau was reached. For the frequency-force relationship, the curve for soleus muscles was merely shifted to the left of that for EDL muscles. In contrast, the power developed by EDL muscles was greater than that of soleus muscles (P less than 0.05) at each stimulation frequency. The higher power was a direct consequence of higher optimum velocities for EDL muscles compared with soleus muscles.     

季节及人工低温对大蟾蜍肌组织ATP酶的影响研究

本文研究了大蟾蜍心肌和腓肠肌肌球蛋白钙激活ATP酶的活性。实验结果显示,大蟾蜍心肌和腓肠肌肌球蛋白钙激话ATP酶活性具有不同的季节变化规律。并且这种酶活性的季节变化不受人工低温环境因素的影响。此外,大蜍蟾心肌中ATP酶的活性始终高于腓肠肌的。上述酶活性的变化均具有一定的生理意义。     

Sarcomere length organization as a design for cooperative function amongst all lumbar spine muscles

The functional design of spine muscles in part dictates their role in moving, loading, and stabilizing the lumbar spine. There have been numerous studies that have examined the isolated properties of these individual muscles. Understanding how these muscles interact and work together, necessary for the prediction of muscle function, spine loading, and stability, is lacking. The objective of this study was to measure sarcomere lengths of lumbar muscles in a neutral cadaveric position and predict the sarcomere operating ranges of these muscles throughout full ranges of spine movements. Sarcomere lengths of seven lumbar muscles in each of seven cadaveric donors were measured using laser diffraction. Using published anatomical coordinate data, superior muscle attachment sites were rotated about each intervertebral joint and the total change in muscle length was used to predict sarcomere length operating ranges. The extensor muscles had short sarcomere lengths in a neutral spine posture and there were no statistically significant differences between extensor muscles. The quadratus lumborum was the only muscle with sarcomere lengths that were optimal for force production in a neutral spine position, and the psoas muscles had the longest lengths in this position. During modeled flexion the extensor, quadratus lumborum, and intertransversarii muscles lengthened so that all muscles operated in the approximate same location on the descending limb of the force-length relationship. The intrinsic properties of lumbar muscles are designed to complement each other. The extensor muscles are all designed to produce maximum force in a mid-flexed posture, and all muscles are designed to operate at similar locations of the force-length relationship at full spine flexion.     

Difference in skeletal muscle function in males vs. females: role of estrogen receptor-beta

Male skeletal muscles are generally faster and have higher maximum power output than female muscles. Conversely, during repeated contractions, female muscles are generally more fatigue resistant and recover faster. We studied the role of estrogen receptor-beta (ERbeta) in this gender difference by comparing contractile function of soleus (mainly slow-twitch) and extensor digitorum longus (fast-twitch) muscles isolated from ERbeta-deficient (ERbeta(-/-)) and wild-type mice of both sexes. Results showed generally shorter contraction and relaxation times in male compared with female muscles, and ERbeta deficiency had no effect on this. Fatigue (induced by repeated tetanic contractions) and recovery of female muscles were not affected by ERbeta deficiency. However, male ERbeta(-/-) muscles were slightly more fatigue resistant and produced higher forces during the recovery period than wild-type male muscles. In fact, female muscles and male ERbeta(-/-) muscles displayed markedly better recovery than male wild-type muscles. Gene screening of male soleus muscles showed 25 genes that were differently expressed in ERbeta(-/-) and wild-type mice. Five of these genes were selected for further analysis: muscle ankyrin repeat protein-2, muscle LIM protein, calsequestrin, parvalbumin, and aquaporin-1. Expression of these genes showed a similar general pattern: increased expression in male and decreased expression in female ERbeta(-/-) muscles. In conclusion, ERbeta deficiency results in increased performance during fatigue and recovery of male muscles, whereas female muscles are not affected. Improved contractile performance of male ERbeta(-/-) mouse muscles was associated with increased expression of mRNAs encoding important muscle proteins.     

Chronic stimulation modifies the isotonic shortening velocity of denervated rat slow-twitch muscle

Rat soleus muscles were denervated and stimulated in vivo for periods of up to 104 days. Stimuli used were trains of 1 ms pulses at 100 Hz delivered for periods of 1 s; trains were repeated every 10-100 s. In a majority of animals the tension of the muscles was maintained at about 10% of normal, equivalent to muscles denervated but unstimulated for 20 days. At the longest periods the stimulated muscles developed ten times more tension than ones that were denervated but not stimulated. In denervated and denervated-stimulated muscles twitch contraction and relaxation times were prolonged, compared with controls, for up to 3 weeks. Thereafter both sets showed a speeding of the isometric twitch that was greater in the stimulated muscles. At the longest periods the twitch was as short as that of a denervated fast muscle. Stimulation did not affect contralateral denervated muscles. Twitch: tetanus ratios remained high despite stimulation, and muscles showed little post-tetanic potentiation. Tension developed more rapidly in the tetani of the stimulated muscles, even allowing for larger final values. Maximum velocity of shortening was increased in many of the stimulated muscles, and there was a proportional flattening of the force-velocity curve, i.e. a/P0 increased. Maximum velocity and a/P0 increased reciprocally with twitch time to peak, so that those muscles that had twitches most changed by stimulation also had their isotonic properties modified to the greatest extent. Even at the longest period of stimulation, twitch time course and tetanic tension were not converted to those of normal fast muscle.     

Muscle grafts overloaded by ablation of synergistic muscles

We hypothesized that the mass and maximum tetanic tension (Po) of nerve-intact grafts overloaded by ablation of synergistic muscles would be greater than that of standard nerve-intact grafts or of control soleus muscles. Soleus muscles were grafted orthotopically and bilaterally in 35 female rats. Control soleus muscles were obtained from 30 age-matched cohorts. Twenty-eight days following grafting, gastrocnemius muscles were ablated bilaterally in half of the animals. Comparisons were made between 28 and 112 days following grafting. By 112 days the wet mass of the overload nerve-intact grafts was 138% of the standard grafts and 152% of the control soleus muscles, whereas the Po was 161% and 107%, respectively. Specific tension stabilized at approximately 19 +/- 1 N/cm2 for both types of grafts, significantly lower than the value of 24 +/- 1 N/cm2 for control soleus muscles. Ablation of synergistic muscles resulted in a significant and sustained increase in mass and Po in regenerating skeletal muscle autografts. We conclude that provided the appropriate conditioning stimulus small grafts (100-200 mg) are capable of achieving the values for the mass and Po of control muscles.     

Effect of stimulation of pulmonary C-fiber receptors on canine respiratory muscles

The effects of stimulation of pulmonary C-fiber receptors on the distribution of motor activity to upper airway, rib cage, and abdominal muscles were studied in anesthetized, tracheotomized, spontaneously breathing dogs. Stimulation of pulmonary C-fiber receptors by injection of capsaicin (3-20 micrograms/kg) into the right atrium resulted in complete cessation of electrical activity of the upper airway dilating muscles (UADM) and the inspiratory chest wall pumping muscles. The activity of abdominal muscles was also inhibited. The duration of electrical silence was longer for the diaphragm than for the UADM. Upper airway constricting muscles and expiratory intercostal muscles, including the triangularis sterni, remained tonically active during the apneic period. The responses of these muscles were qualitatively the same when the animals breathed 100% O2, 7% CO2 in O2, or 12% O2 in N2, and without or in the presence of an expiratory threshold load. Bilateral vagotomy abolished the inhibitory effects of capsaicin on UADM, chest wall, and abdominal muscle activity, suggesting that the vagus is the major afferent pathway for the reflex. The qualitative difference in the response of intercostal expiratory muscles and abdominal muscles suggests that these two groups of synergistic muscles may be independently regulated.     

Theoretical considerations on cocontraction of sets of agonistic and antagonistic muscles

It is well known that static, non-linear minimization of the sum of the stress in muscles to a certain power cannot predict cocontraction of pairs of one-joint antagonistic muscles. In this report, we prove that for a single joint either all agonistic muscles cocontract or all are silent. For two-joint muscles, we show that lengthening and shortening of muscles corresponds closely to zero force and non-zero force states, respectively. This gives a new physiological interpretation of situations in which cocontraction of pairs of two-joint antagonistic muscles is predicted by these static non-linear optimization approaches.     

Cellular and molecular responses to increased skeletal muscle loading after irradiation

Irradiation of rat skeletal muscles before increased loading has been shown to prevent compensatory hypertrophy for periods of up to 4 wk, possibly by preventing satellite cells from proliferating and providing new myonuclei. Recent work suggested that stem cell populations exist that might allow irradiated muscles to eventually hypertrophy over time. We report that irradiation essentially prevented hypertrophy in rat muscles subjected to 3 mo of functional overload (OL-Ir). The time course and magnitude of changes in cellular and molecular markers of anabolic and myogenic responses were similar in the OL-Ir and the contralateral nonirradiated, overloaded (OL) muscles for the first 3-7 days. These markers then returned to control levels in OL-Ir muscles while remaining elevated in OL muscles. The number of myonuclei and amount of DNA were increased markedly in OL but not OL-Ir muscles. Thus it appears that stem cells were not added to the irradiated muscles in this time period. These data are consistent with the theory that the addition of new myonuclei may be required for compensatory hypertrophy in the rat.     

Paradoxical absence of M lines and downregulation of creatine kinase in mouse extraocular muscle.

The M lines are structural landmarks in striated muscles, necessary for sarcomeric stability and as anchoring sites for the M isoform of creatine kinase (CK-M). These structures, especially prominent in fast skeletal muscles, are missing in rodent extraocular muscle, a particularly fast and active muscle group. In this study, we tested the hypotheses that 1). myomesin and M protein (cytoskeletal components of the M lines) and CK-M are downregulated in mouse extraocular muscle compared with the leg muscles, gastrocnemius and soleus; and 2). the expression of other cytosolic and mitochondrial CK isoforms is correspondingly increased. As expected, mouse extraocular muscles expressed lower levels of myomesin, M protein, and CK-M mRNA than the leg muscles. Immunocytochemically, myomesin and M protein were not detected in the banding pattern typically seen in other skeletal muscles. Surprisingly, message abundance for the other known CK isoforms was also lower in the extraocular muscles. Moreover, total CK activity was significantly decreased compared with that in the leg muscles. Based on these data, we reject our second hypothesis and propose that other energy-buffering systems may be more important in the extraocular muscles. The downregulation of major structural and metabolic elements and relative overexpression of two adenylate kinase isoforms suggest that the extraocular muscle group copes with its functional requirements by using strategies not seen in typical skeletal muscles.     

Differentiation of a Male-Specific Muscle in Drosophila Melanogaster Does Not Require the Sex-Determining Genes Doublesex or Intersex

A pair of muscles span the fifth abdominal segment of male but not female Drosophila melanogaster adults. To establish whether genes involved in the development of other sexually dimorphic tissues controlled the differentiation of sex-specific muscles, flies mutant for five known sex-determining genes were examined for the occurrence of male-specific abdominal muscles. Female flies mutant for alleles of Sex-lethal, defective in sex determination, or null alleles of transformer or transformer-2 are converted into phenotypic males that formed male-specific abdominal muscles. Both male and female flies, when mutant for null alleles of doublesex, develop as nearly identical intersexes in other somatic characteristics. Male doublesex flies produced the male-specific muscles, whereas female doublesex flies lacked them. Female flies, even when they inappropriately expressed the male-specific form of doublesex mRNA, failed to produce the male-specific muscles. Therefore, the wild-type products of the genes Sex-lethal, transformer and transformer-2 act to prevent the differentiation of male-specific muscles in female flies. However, there is no role for the genes doublesex or intersex in either the generation of the male-specific muscles in males or their suppression in females.     

Functional relationship between the foot intrinsic and extrinsic muscles in walking

The intrinsic and extrinsic muscles are considered to stabilize the foot and contribute to propulsion during walking. This study aimed to clarify the functional relationship between intrinsic and extrinsic muscles during walking. Thirteen healthy men participated in this study. The muscle activities of the intrinsic muscles (quadratus plantae and abductor hallucis), and the extrinsic muscles (flexor hallucis longus, flexor digitorum longus, and tibialis posterior) were measured using fine-wire and surface electromyography during walking. The muscle onset timing after foot contact was calculated and compared among muscles using the one-way ANOVA. The stance phase was divided into early and late braking, and early and late propulsion phases. Muscle activity among phases was compared using repeated-measures ANOVA. The onset time of the abductor hallucis was significantly earlier than those of the flexor digitorum longus and tibialis posterior. The quadratus plantae demonstrated significantly earlier onset than that of the tibialis posterior. In the late propulsion phase, the activity of extrinsic muscles decreased, whereas intrinsic muscles were continuously active. Early activation of the intrinsic muscles may stabilize the foot for efficient torque production by the extrinsic muscles. Furthermore, the intrinsic muscles may contribute to the final push-off after the deactivation of extrinsic muscles.