Why are fetal muscles slow?

Differentiating fast and slow mammalian muscles contract slowly at birth and increase their speed during the first few weeks of life. However, only small proportions of slow myosin light chains are found in early developing muscles and the fast type of light chains predominate. In addition, differentiating muscle contains unique, embryonic forms of myosin which may partially determine the early slow responses. The present study suggests additional reasons for these slow twitch times. Most skeletal muscles are initially formed from a small population of primary generation cells which are innervated by pioneering axons early in myogenesis. Subsequently, numerous secondary generation cells develop along the walls of primary myotubes, then separate and become independent units of contraction. Using affinity-purified antibodies to fast and slow myosin, it was found that most primary myotubes react with anti-slow myosin and are destined to become slow, Type I fibres. By contrast, secondary generation cells stain exclusively with anti-fast myosin and develop into Type II, fast fibres. We propose that primary myotubes constitute the fundamental motor units of the developing neuromuscular system and are responsible for early slow movements. Secondary generation cells become organized into large, fast motor units later in development, eclipsing the original slow response.     

Acetylcholinesterase mRNA level and synaptic activity in rat muscles depend on nerve-induced pattern of muscle activation

Acetylcholinesterase (AChE) mRNA levels are severalfold higher in fast rat muscles compared with slow. We hypothesized that AChE mRNA levels and AChE activity in the neuromuscular junction depend on a specific nerve-induced pattern of motor unit activation. Chronic low-frequency stimulation, mimicking the activation pattern in slow muscles, was applied to fast muscles in rats. Molecular forms of AChE were analyzed by velocity sedimentation, and AChE mRNA levels were analyzed by Northern blots. AChE mRNA levels in stimulated fast muscles dropped to 10-20% of control after 1 week and became comparable to those in slow soleus muscles. The activity of the junctional A12 AChE form in 35 d stimulated fast muscles decreased to 56% of control value, reaching that in the soleus muscle. Therefore, synaptic AChE itself depends on the muscle activation pattern. Complete inactivity after denervation also decreased the AChE mRNA level in fast muscles to <10% in 48 hr. In contrast, profuse fibrillations observed in noninnervated immature regenerating muscles maintain AChE mRNA levels at 80% of that in the innervated fast muscles. If protein synthesis was inhibited by cycloheximide, AChE mRNA levels in 3-d-old regenerating muscle, still containing myoblasts, increased approximately twofold. No significant increase after cycloheximide application was observed either in denervated mature fast muscles or in normal slow muscles. Low AChE mRNA levels observed in those muscles are probably not caused by decreased stability of AChE mRNA as demonstrated in myoblasts.     

The structural basis of molecular adaptation

Expression levels of fast-twitch (SERCA1), slow-twitch (SERCA2a) and "housekeeping" (SERCA2b) isoforms of the sarcoplasmic reticulum Ca(2+)-transport ATPase were monitored during regeneration of rat soleus muscles following necrosis induced by the toxin notexin at the tissue level by Western blot analysis and at the cellular level by immunocytochemical analysis. Due to necrosis, levels of muscle-specific SERCA1 and SERCA2a isoforms dropped to low levels on the third day after injection of the toxin. Subsequently, during regeneration both isoforms recovered but with a different time course. Expression of the fast type SERCA1 increased first. This type showed its most pronounced increase between day 3 and 10. Expression of the slow type SERCA2a was biphasic. After an increase to approximately one third of the control value on days 5-10, it showed its main increase up to the control level between day 10 and 21. Expression levels of the house-keeping SERCA2b isoform remained relatively constant throughout the 4 weeks of regeneration. Between day 10 and 28, when new innervation is established, SERCA2a expression spread gradually over almost all fibers whereas the number of SERCA1-expressing fibers decreased and only a limited number of fibers co-expressed SERCA1 and SERCA2a. At 4 weeks of regeneration, expression of the fast isoform was found only in 12% of the fibers, whereas the slow form was found in 98% of the fibers. In the contralateral untreated soleus muscles, 26% SERCA1-positive and 81% SERCA2a-positive fibers were observed. Immunocytochemical analysis showed that SERCA1 and SERCA2a were co-expressed with fast and slow myosin isoforms in fibers of normal muscles but in regenerated muscle only slow myosin and slow SERCA isoforms correlated. The results show that during regeneration levels of fast and slow SERCA proteins change in a similar way as their mRNAs do. However, in regenerated soleus, unlike in normal muscle, expression of slow SERCA is coregulated only with the slow myosin isoform. This finding is in agreement with the fact that the number of slow type fibers is increased in regenerated soleus.     

Murine endodermal F9E cells, derived from the teratocarcinoma line F9, contain high basal levels of retinoic acid receptors (RARs and RXRs) but are not sensitive to the actions of retinoic acid

We observed differences in the capillary architecture of the skeletal muscles that have different fiber metabolism. The soleus, the vastus intermedius and the tibialis anterior muscles of adult Wistar rats were prepared using two different techniques. Samples for adenosine triphosphatase (ATPase) staining were prepared following Dubovitz's method, and the distributions of fiber type, Types 1, 2A and 2B, were analyzed. Then, corrosion casts of capillary architecture of these muscles prepared following Murakami's method were observed with a scanning electron microscope (SEM) and compared with the fiber distribution. The fiber type composition of the soleus muscle showed Type 1 (slow-twitch) dominance and that of the vastus intermedius and the tibialis anterior muscle showed Type 2 (fast-twitch) dominance. The capillaries of the soleus muscle were tortuous, and this was thought to be advantageous for blood supply. In contrast, the capillaries of the vastus intermedius and tibialis anterior muscles had a relatively parallel pattern. Additionally, two different patterns of capillary architecture that appeared to correspond to certain metabolic characteristic of different muscle fiber types were preserved with corrosion casting. In conclusion, comparative studies on capillary architecture of the skeletal muscles are useful for analyses of its function.     

Expression of myosin heavy chain and of myogenic regulatory factor genes in fast or slow rabbit muscle satellite cell cultures

We investigated the myogenic properties of rabbit fast or slow muscle satellite cells during their differentiation in culture, with a particular attention to the expression of myosin heavy chain and myogenic regulatory factor genes. Satellite cells were isolated from Semimembranosus proprius (slow-twitch muscle; 100% type I fibres) and Semimembranosus accessorius (fast-twitch muscle; almost 100% type II fibres) muscles of 3-month-old rabbits. Satellite cells in culture possess different behaviours according to their origin. Cells isolated from slow muscle proliferate faster, fuse earlier into more numerous myotubes and mature more rapidly into striated contractile fibres than do cells isolated from fast muscle. This pattern of proliferation and differentiation is also seen in the expression of myogenic regulatory factor genes. Myf5 is detected in both fast or slow 6-day-old cell cultures, when satellite cells are in the exponential stage of proliferation. MyoD and myogenin are subsequently detected in slow satellite cell cultures, but their expression in fast cell cultures is delayed by 2 and 4 days respectively. MRF4 is detected in both types of cultures when they contain striated and contractile myofibres. Muscle-specific myosin heavy chains are expressed earlier in slow satellite cell cultures. No adult myosin heavy chain isoforms are detected in fast cell cultures for 13 days, whereas cultures from slow cells express neonatal, adult slow and adult fast myosin heavy chain isoforms at that time. In both fast and slow satellite cell cultures containing striated contractile fibres, neonatal and adult myosin heavy chain isoforms are coexpressed. However, cultures made from satellite cells derived from slow muscles express the slow myosin heavy chain isoform, in addition to the neonatal and the fast isoforms. These results are further supported by the expression of the mRNA encoding the adult myosin heavy chain isoforms. These data provide further evidence for the existence of satellite cell diversity between two rabbit muscles of different fibre-type composition, and also suggest the existence of differently preprogrammed satellite cells.     

Consequences of the combined deficiency in dystrophin and utrophin on the mechanical properties and myosin composition of some limb and respiratory muscles of the mouse

The mechanical properties and the myosin isoform composition were studied in three isolated muscles (EDL, soleus, diaphragm) of mutant mice lacking both dystrophin and utrophin (dko). They were compared with the corresponding muscles of the normal and the dystrophin-deficient (mdx) and the utrophin-deficient (uko) mice. In comparison with mdx muscles, dko muscles show a significant reduction of the normalized isometric force, confirmed by the reduced muscular activity of the whole animal. Kinetics parameters (twitch time-to-peak and half-relaxation time) were slightly reduced, and the maximal speed of shortening of soleus, Vmax, was reduced by 30%. The maximal power output (muW/mm3) was reduced by 50% in dko soleus. In the three muscles studied, the relative myosin heavy chains (MHC) composition showed a shift towards slower isoforms. dko EDL presented a dramatic decrease of the resistance ot tetanic contraction with forced lengthenings (eccentric contractions), while muscle lacking only utrophin (uko mutants) display a normal resistance to this exacting mechanical challenge. These experiments suggest that lack of both dystrophin and utrophin is very detrimental to the mice and that mechanical properties of the muscles may explain the overall phenotype. Moreover these results bring some support to the idea that the expression of utrophin in mdx muscle compensates, to some extent, for the lack of dystrophin.     

Force and myosin content variation in isolated intact single muscle fibres from Rana temporaria

We studied the relation between force normalized by dry mass per unit length and the myosin fraction of muscle dry mass. The two tibialis anterior muscles were dissected from 12 frogs (Rana temporaria). Then, from one muscle, two single fast-twitch fibres were isolated. Each fibre was mounted isometrically in Ringer's solution, and electrically stimulated using a standardized protocol. Peak force production, normalized by the fibre's dry mass per unit length, varied by a factor of 1.4. Little variation in normalized force was measured between fibres from the same animal, whereas between animals a significant difference was found (P<0.05). The contralateral muscle was used to determine the myosin fraction of the dry mass. The relationship between the fraction myosin of the dry mass and force normalized by dry mass per unit length showed a high correlation (r = 0.81; n = 12). From this we conclude that variation in normalized tetanic force is determined greatly (65%) by variations in myosin content.     

Differential effects of a six-day immobilization on newborn rat soleus muscles at two developmental stages

Our objective was to determine the effects of a six-day immobilization on the musculoskeletal system of the rat during postnatal development at two key periods when the states of innervation are known to be different. This work was undertaken on the soleus muscle since it is well known that postural slow muscles show marked changes after a period of disuse. Thus, the soleus muscle was immobilized in a shortened position either when the innervation was polyneuronal or monosynaptic, respectively from 6 to 12 and from 17 to 23 days. The muscle modifications were followed by ATPase staining and myosin heavy chain (MyHC) isoform identification using monoclonal antibodies and SDS-PAGE. The functional properties of skinned fibre bundles were established by calcium/strontium (Ca/Sr) activation characteristics. In control muscles the maturation was characterized by a progressive increase of adult MyHCs (I and IIA) concomitant with a decrease in both the MyHC neo and the Ca affinity. Between 6 to 12 days, immobilization of the limb induced an increase in histochemical type IIC fibres. Using antibodies we identified new fibre types, classified as a function of their MyHC isoform co-expression. We observed an increase in expression of both MyHC neo and Ca affinity. From 17 to 23 days, the immobilization induced an increase in Ca affinity and marked changes in the MyHC isoform composition: disappearance of MyHC neo and expression of the fast MyHC IIB isoform, which in normal conditions is never expressed in the soleus muscle. We conclude that an immobilization imposed during polyneuronal innervation delays the postnatal maturation of the soleus muscle, whereas when the immobilization is performed under monosynaptic innervation the muscle evolves towards a fast phenotype using a default pathway for MyHC expression.     

Cardiomyoplasty - improvement of muscle fibre type transformation by an anabolic steroid (metenolone)

Dynamic cardiomyoplasty, a method to support ventricular function by the chronically stimulated latissimus dorsi muscle wrapped around the heart is accompanied by a loss of mass and force of the transplanted muscle. These effects and the fast-to-slow transformation of the muscle could be possibly influenced by the additional administration of anabolic steroids. In this study, the left latissimus dorsi muscles of 12 sheep were electrically conditioned (group A). In 12 other animals (group B), stimulation was combined with the administration of metenolone (100 mg/week). Biopsies were taken from the right and left muscles at the beginning and after 6 and 12 weeks of treatment, frozen and cross-sectioned. The muscle fibre type composition was studied enzymhistochemically (SDH-staining and Myosin-ATPase-reaction) and immunocytochemically (using antibodies against different myosin heavy chains, MHC). Furthermore, the expression of different MHC isoforms was investigated electrophoretically. The untreated latissimus dorsi muscle contains 20% type I fibres expressing slow MHC and 80% type II fibres expressing fast MHC. After 6 weeks, the respective fibre type composition was 42 and 58% (group A) and 80 and 20% (group B). After 12 weeks, the percentage of the type I fibres rose in group A to 59% and in group B to 98%. In accordance with these morphological results, the MHC pattern determined electrophoretically showed a corresponding shift from the fast to the slow isoform. Therefore, the administration of metenolone avoids severe muscle atrophy, and improves and accelerates fast to slow fibre type conversion necessary for successful cardiomyoplasty.     

Neuromuscular blocking effects of aminoglycoside antibiotics on fast- and slow-contracting muscles of the cat

The neuromuscular-blocking effects of neomycin, streptomycin, and gentamicin were examined in fast- and slow-twitch muscles of pentobarbital-anesthetized cats. These antibiotics were more effective in reducing indirectly stimulated contractions of the gastrocnemius muscle than of the ipsilateral soleus muscle in adult cats. Respiratory-depressant effects of these antibiotics were more closely associated temporally with effects on soleus than on gastrocnemius twitch. Neomycin was a more potent neuromuscular blocking agent in kittens greater than 7 weeks old than in kittens less than 6 weeks old. Calcium ions were more effective in antagonizing the effects of neomycin on gastrocnemius than on soleus twitch; however, neostigmine was more effective in antagonizing the effects of neomycin on soleus than on gastrocnemius twitch. These data indicate a difference in responsiveness of fast- and slow-twitch muscles (fast greater than slow) to the neuromuscular-blocking effects of aminoglycoside antibiotics, and suggest that this may be related to a difference in the predominance of pre- and postjunctional inhibitory actions of these agents in the 2 muscle types.     

Experimental muscle pain increases the human stretch reflex

In this study we investigated the effect of human experimental muscle pain on H- and stretch reflexes as indicators of changes in muscle spindle sensitivity. Fourteen healthy, male volunteers participated in the study. Muscle pain was produced by infusion of 5% hypertonic saline over a period of 10-15 min in m. soleus and in m. tibialis anterior. Reflexes were elicited in the relaxed and active soleus muscle (10-15 Nm ankle torque) before, during and after muscle pain. Control measurements were made with infusions of 0.9% isotonic saline. Surface electromyograms (EMG) were measured from the soleus muscle, and torque was measured from the ankle joint. With pain in the soleus muscle the mechanical stretch reflex response (ankle torque) increased significantly (P = 0.0007) as compared to before pain. With pain in the tibialis anterior muscle both the mechanical and EMG responses increased significantly (P = 0.001; P = 0.0003) as compared to before pain. The H-reflex showed no significant changes during the infusions in either muscles. This study has demonstrated a muscle pain-related increase in the amplitude of the stretch reflex without a corresponding increase in the H-reflex amplitude. One explanation could be an increased dynamic sensitivity of the muscle spindles during muscle pain caused by an increased firing rate in the dynamic gamma-motoneurones. However, the data could not support the vicious cycle model because the excitability of the alpha-motoneurone pool was unchanged.     

Cellular adaptations in the diaphragm in chronic obstructive pulmonary disease

BACKGROUND: In patients with severe chronic obstructive pulmonary disease, the diaphragm undergoes physiologic adaptations characterized by an increase in energy expenditure and relative resistance to fatigue. We hypothesized that these physiologic characteristics would be associated with structural adaptations consisting of an increased proportion of less-fatigable slow-twitch muscle fibers and slow isoforms of myofibrillar proteins. METHODS: We obtained biopsy specimens of the diaphragm from 6 patients with severe chronic obstructive pulmonary disease (mean [+/-SE] forced expiratory volume in one second, 33+/-4 percent of the predicted value; residual volume, 259+/-25 percent of the predicted value) and 10 control subjects. The proportions of the various isoforms of myosin heavy chains, myosin light chains, troponin, and tropomyosin were determined by sodium dodecyl sulfate-polyacrylamide-gel electrophoresis. We also used immunocytochemical techniques to determine the proportions of the various types of muscle fibers. RESULTS: The diaphragm-biopsy specimens from the patients had higher percentages of slow myosin heavy chain I (64+/-3 vs. 45+/-2 percent, P<0.001), and lower percentages of fast myosin heavy chains IIa (29+/-3 vs. 39+/-2 percent, P=0.01) and IIb (8+/-1 vs. 17+/-1 percent, P<0.001) than the diaphragms of the controls. Similar differences were noted when immunohistochemical techniques were used to compare the percentages of these fiber types in the two groups. In addition, the patients had higher percentages of the slow isoforms of myosin light chains, troponins, and tropomyosin, whereas the controls had higher percentages of the fast isoforms of these proteins. CONCLUSIONS: Severe chronic obstructive pulmonary disease increases the slow-twitch characteristics of the muscle fibers in the diaphragm, an adaptation that increases resistance to fatigue.     

Molecular forms of acetylcholinesterase in dystrophic (mdx) mouse tissues

We analyzed the activity of acetylcholinesterase (AChE) and its molecular forms in the tissues of normal and dystrophic (mdx) mice, at different developmental stages. We studied the brain, the heart and the serum, in addition to four predominantly fast-twitch muscles (tibialis, plantaris, gastrocnemius and extensor digitorum longus (EDL)) and the slow-twitch, soleus muscle. We found no difference between mdx and control mice in the AChE activity of the brain and the heart. The skeletal muscles affected by the disease undergo active degeneration counterbalanced by regeneration between 3 and 14 weeks after birth. The distribution of AChE patches associated with neuromuscular junctions was abnormally scattered in mdx muscles, and in some cases (tibialis and soleus), the number of endplates was more than twice that of normal muscles. There were only minor differences in the concentration and pattern of AChE molecular forms during the acute phase of muscle degeneration and regeneration. After this period, however, we observed a marked deficit in the membrane-bound G4 molecular form of AChE in adult mdx tibialis, gastrocnemius and EDL but not in the plantaris or in the soleus, as compared with their normal counterparts. Whereas the amount of AChE markedly decreased in the serum of normal mice during the first weeks of life, it remained essentially unchanged in the serum of mdx mice. It is likely that this excess of AChE activity in serum originates from the muscles. A deficit in muscle G4 was also reported in other forms of muscular dystrophy in the mouse and chicken. Since it is not correlated to the acute phase of the disease in mdx and also occurs in genetically different dystrophies, it probably represents a secondary effect of the dystrophy.     

Muscle unloading induces slow to fast transitions in myofibrillar but not mitochondrial properties. Relevance to skeletal muscle abnormalities in heart failure

Muscle deconditioning is a common observation in patients with congestive heart failure (CHF), chronic obstructive pulmonary disease, neuromuscular diseases or prolonged bed rest. To gain further insight into metabolic and mechanical properties of deconditioned slow-twitch (soleus) or fast-twitch (EDL) skeletal muscles, we induced experimental muscle deconditioning by hindlimb suspension (HS) in rats for 3 weeks. Cardiac muscle was also studied. Besides profound muscle atrophy, increased proportion of fast type II fibers as well as fast myosin isoenzymes, we found decreased calcium sensitivity of Triton X-100 skinned fiber bundles of soleus muscle directed towards the fast muscle phenotype. Glycolytic enzymes such as hexokinase and pyruvate kinase were increased, and the LDH isoenzyme pattern was clearly shifted from an oxidative to an anaerobic profile. Creatine kinase (CK) and myokinase activities were increased in HS soleus towards EDL values. Moreover, the M-CK mRNA level was greatly increased in soleus, with no change in EDL. However, oxygen consumption rate assessed in situ in saponin skinned fibers (12.5 +/- 0.8 in C and 15.1 +/- 0.9 micromol O2/min/g dw in HS soleus compared to 7.3 +/- 1.3 micromol O2/min/g dw in control EDL), as well as mitochondrial CK (mi-CK) and citrate synthase activities, were preserved in HS soleus. Following deconditioning no change in Km for ADP of mitochondrial respiration, either in the absence (511 +/- 92 in C and 511 +/- 111 microM in HS soleus compared to 9 +/- 4 microM in control EDL) or presence of creatine (88 +/- 10 in C and 95 +/- 16 microM in HS soleus compared to 32 +/- 9 microM in control EDL), was found. The results show that muscle deconditioning induces a biochemical and functional slow to fast phenotype transition in myofibrillar and cytosolic compartments of postural muscle, but not in the mitochondrial compartment, suggesting that these compartments are differently regulated under conditions of decreased activity.     

Interorgan signaling between adipose tissue metabolism and skeletal muscle uncoupling protein homologs: is there a role for circulating free fatty acids?

Uncoupling proteins 3 and 2 (UCP3 and UCP2) are two newly cloned genes that have been implicated in the regulation of lipids as fuel substrate in skeletal muscle on the basis that their mRNA expressions are upregulated during starvation (when fat stores are being rapidly mobilized) and downregulated during the early phase of refeeding (when fat stores are being rapidly replenished). To test the hypothesis that circulating free fatty acids (FFAs) may have a physiological role as an interorgan signal linking these dynamic changes in the fat stores to skeletal muscle expression of UCP3 and UCP2, the mRNA levels of these UCP homologs were examined in fed and fasted rats treated with the antilipolytic agent nicotinic acid. In 46-h fasted rats, we observed a threefold increase in serum FFA levels and increases in UCP3 and UCP2 mRNA levels that were more marked in the gastrocnemius and tibialis anterior muscles (predominantly fast-twitch fibers) than in the soleus muscle (predominantly slow-twitch fibers). Treatment with nicotinic acid blunted the fasting-induced increase in serum FFA levels and prevented the increase in mRNA levels of UCP3 and UCP2 in the soleus muscle, but had little or no effect on the elevated mRNA levels of these UCP homologs in the gastrocnemius and tibialis anterior muscles. Furthermore, treatment of ad libitum-fed animals with nicotinic acid resulted in a twofold reduction in serum FFA levels (i.e., by a magnitude similar to that observed during early refeeding) and significant reductions in UCP3 and UCP2 mRNA levels in the soleus muscle, but not in the gastrocnemius or tibialis anterior muscles. These results revealed a muscle-type dependency in the way UCP2 and UCP3 gene expression in skeletal muscle is regulated, and suggest that the hypothesis that circulating FFAs function as an interorgan signal between fat stores and skeletal muscle UCP3 and UCP2 gene expression is adequate only for slow-twitch (oxidative) muscles. Consequently, a signal(s) other than circulating FFAs must be implicated in the link between dynamic changes in body fat stores and UCP expression in predominantly fast-twitch (glycolytic/oxidative-glycolytic) muscles, which constitute the major fiber type of the total skeletal muscle mass and which have high susceptibility to developing insulin resistance and impairment in substrate utilization in metabolic diseases.     

Differential myogenicity of satellite cells isolated from extensor digitorum longus (EDL) and soleus rat muscles revealed in vitro

Following muscle damage, fast- and slow-contracting fibers regenerate, owing to the activation of their satellite cells. In rats, crush-induced regeneration of extensor digitorum longus (EDL, a fast muscle) and soleus (a slow muscle) present different characteristics, suggesting that intrinsic differences exist among their satellite cells. An in vitro comparative study of the proliferation and differentiation capacities of satellite cells isolated from these muscles is presented there. We observed several differences between soleus and EDL satellite cell cultures plated at high density on gelatin-coated dishes. Soleus satellite cells proliferated more actively and fused into myotubes less efficiently than EDL cells. The rate of muscular creatine kinase enzyme appeared slightly lower in soleus than in EDL cultures at day 11 after plating, when many myotubes were formed, although the levels of muscular creatine kinase mRNA were similar in both cultures. In addition, soleus cultures expressed higher levels of MyoD and myogenin mRNA and of MyoD protein than EDL satellite cell cultures at day 12. A clonal analysis was also carried out on both cell populations in order to determine if distinct lineage features could be detected among satellite cells derived from EDL and soleus muscles. When plated on gelatin at clonal density, cells from both muscles yielded clones within 2 weeks, which stemmed from 3-15 mitotic cycles and were classified into three classes according to their sizes. Myotubes resulting from spontaneous fusion of cells from the progeny of one single cell were seen regardless of the clone size in the standard culture medium we used. The proportion of clones showing myotubes in each class depended on the muscle origin of the cells and was greater in EDL- than in soleus-cell cultures. In addition, soleus cells were shown to improve their differentiation capacity upon changes in the culture condition. Indeed, the proportions of clones showing myotubes, or of cells fusing into myotubes in clones, were increased by treatments with a myotube-conditioned medium, with phorbol ester, and by growth on extra-cellular matrix components (Matrigel). These results, showing differences among satellite cells from fast and slow muscles, might be of importance to muscle repair after trauma and in pathological situations.     

Fiber-type-specific expression of essential (alkali) myosin light chains in human skeletal muscles

We studied the expression patterns of the essential (alkali) myosin light-chain isoforms in adult human skeletal muscles, using in situ hybridization and single-fiber protein analysis. In analogy to other species, we found that the fiber type-specific expression of essential myosin light chains is regulated via the availability of the respective mRNAs in a given fiber. In contrast to other species, the slow isoform 1sa was only expressed in the most oxidative Type I fibers (Subtype IA) in addition to 1sb. These fibers also contained high levels of carbonic anhydrase III. Within the fibers, the essential myosin light-chain mRNAs were located preferentially in the perinuclear regions and to a lesser extent in the intermyofibrillar spaces, a distribution that excludes cotranslational assembly of these light chains into the myofibrils as the main mechanism. In comparing leg and shoulder muscles, we found less distinct fiber typing in the expression patterns of the essential myosin light chains in the leg muscles than in muscles from the shoulder region.     

Modulation of H reflexes in human tibialis anterior muscle with passive movement

Significant movement-induced gain changes in H reflexes have been observed in soleus muscle following passive movement of the lower limb. Hypotheses from these concepts were tested on magnitudes of H reflexes in tonically contracted tibialis anterior. From eleven subjects at rates of 20 and 60 r.p.m. passive leg movement, statistically significant attenuation from controls and phasic modulation occurred. The results make more general the conclusions from soleus H reflexes. However, the functional effect should be much smaller, as tibialis anterior H reflexes are smaller compared to those in soleus.