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PubMed1991

The development of adult muscles in Drosophila: ablation of identified muscle precursor cells.

A small subset of mesodermal cells continues to express twist in the late embryo of Drosophila. These cells are the precursors of adult muscles. Each late twist-expressing cell begins to divide early in the second larval instar and division continues throughout the second and third instars, resulting in a small clone of twist-expressing cells at puparium formation. Treatment with a DNA-synthesis inhibitor, hydroxyurea (HU), ablates these cells if applied during S-phase of their replication cycle. We ablated twist-expressing lineages in the larva and demonstrated that this results in the absence of subsets of muscles in the adult abdomen and leg. HU treatment during this larval period has no discernible effect on the adult epidermis or innervation. We conclude that the twist-expressing cells identified in the late embryo are the unique primordia of adult muscles. Each primordium is fated to establish 6-10 adult muscle fibres, defined here as a 'muscle fibre group'. Each primordium has a unique fate and, after ablation, is not replaced by neighbouring cells. This unique fate does not rest with a particular founder cell within the primordium but is specified at the primordium level: ablation of a subset of cells within a muscle primordium does not result in an ablation of the resulting muscle group or in a decrease in the number of fibres within that muscle group, but rather results in a uniform decrease in the number of nuclei/fibres throughout the entire muscle. Thus, the twist-expressing primordia in the abdomen appear to be fated to give rise to a particular muscle group but act as an equivalent precursor pool in the formation of that muscle group. Our results permit the conclusion that specific muscle groups in the adult leg arise from restricted pools of twist-expressing adepithelial cells in the larval imaginal disc in a similar fashion. We conclude that the fate restriction of myoblast pools in early development defines elements of the final adult muscle pattern. The fate restriction of myoblast cells may be a result of genetic determination to form a specified muscle group or, alternatively, reflect the spatial isolation of otherwise equivalent cells to form muscle-specific precursor pools.

Abdomen↗
PubMed1990

Neuromuscular junctions shrink and expand as muscle fiber size is manipulated: in vivo observations in the androgen-sensitive bulbocavernosus muscle of mice.

Neuromuscular synapses in an androgen-sensitive muscle of sexually mature male mice were repeatedly observed over several-month intervals in normal animals and in animals in which testosterone levels were manipulated. In normal bulbocavernosus muscles, pre- and postsynaptic regions of neuromuscular junctions enlarge as muscle fibers grow. After castration, junctional area decreased in parallel with muscle fiber atrophy. When testosterone was resupplied to castrated animals, junctions that previously decreased in size then enlarged in parallel with muscle fiber hypertrophy. Surprisingly, these size changes occurred without loss or addition of motor nerve terminal branches or acetylcholine (ACh) receptor regions. Rather, each nerve terminal branch and underlying receptor region became smaller following castration and reenlarged following testosterone treatment. Several lines of evidence argued that the size changes observed after castration and testosterone treatment were secondary to shrinkage and stretching of the postsynaptic muscle fiber membrane. Following castration, the spaces between synaptic regions decreased in size at the same time and to a similar extent as the regions themselves. Following testosterone replacement, the spaces between synaptic regions expanded and each existing ACh receptor region enlarged. Ultrastructural analysis showed that there was no loss or addition of postsynaptic secondary junctional folds in the muscle fiber membrane (where ACh receptors are located) as junctions shrank and expanded. Rather, folds became more densely packed as muscle fibers atrophied following castration and less densely packed as muscle fibers hypertrophied following testosterone replacement. From these studies of the bulbocavernosus muscle, as from our previous studies of the sternomastoid muscle, we conclude that neuromuscular junction size is directly coupled to muscle fiber size. Androgens modulate muscle fiber volume directly, leading to a change in the surface area of the muscle fiber membrane, which in turn causes the postsynaptic specializations to shrink or expand. The concomitant shrinkage and stretching of motor nerve terminals that we observed can only be accounted for by their adhesion to postsynaptic specializations that are also changing size. Thus adhesion, rather than an interchange of diffusible factors, trophic or otherwise, is likely to be the primary determinant of coordinated pre- and postsynaptic enlargement in growing mammalian skeletal muscles.

Androgens↗
PubMed1989

[Changes in concentrations of nerve- and muscle-related proteins during reinnervation of slow and fast muscles].

The concentration of the nerve-related (gamma-enolase) and muscle-related (beta-enolase and creatine kinase of B type) proteins was measured in the rat sciatic nerve and the muscles; soleus (SOL), a typical slow-twitch muscle, and extensor digitorum longus (EDL), a typical fast-twitch muscle. The nerves and muscles were subjected to experimental manipulation of their innervation. 1. Nerve-related protein, gamma-enolase. The concentration of gamma-enolase in the distal part of the transected sciatic nerve was decreased in 2 weeks to about 10% of normal. When the sciatic nerve was sutured immediately after the transection, the concentration of gamma-enolase recovered in 34 weeks to a level of about 62.8% of normal. 2. Fast muscle-related protein, beta-enolase. The concentration of the beta-enolase in the SOL and the EDL was reduced after sciatic nerve transection. When the sciatic nerve was sutured immediately after complete transection, the concentration of beta-enolase of SOL and EDL became almost equal on the 34th week. After cross union of the nerves innervating the SOL and EDL muscles, the concentration of the beta-enolase were almost equal on the 20th post-operative week in the both muscles, and reversed on the 34th week. The beta-enolase concentrations in the SOL and EDL muscles innervated by the TTX-perfused sciatic nerve were reduced to 72.3% and 70.4%, respectively. Continuous electrical stimulation of the sciatic nerve reduced the beta-enolase concentration in the EDL to 51.8% of normal, but did not affect the SOL significantly. 3. Slow muscle-related protein, creatine kinase of B type (CK-B). After complete severance of the sciatic nerve the CK-B concentration showed a marked increase in the both muscles. When the sciatic nerve was sutured immediately after transection, the CK-B concentration on the 34th week was about 35.3% in the SOL and close to normal in the EDL. On the 34th week after cross union of the nerves innervating the SOL and EDL muscles, the CK-B concentration was reduced to about 41.1% in the SOL, while it was increased to about 111% in the EDL. On the 20th week after self re-union of the nerves innervating the SOL and EDL muscles, the CK-B concentration in the EDL recovered the normal level, but in the SOL muscle it was increased significantly. 4. It appears that the measurement of the concentration of gamma-enolase, beta-enolase and CK-B can provide valuable informations on the recovery course of skeletal muscles after nerve injury.

Animals↗
PubMed1997

Primary human muscle satellite cell culture: variations of cell yield, proliferation and differentiation rates according to age and sex of donors, site of muscle biopsy, and delay before processing.

The present study was performed to determine the influence on human satellite cell yield, proliferation, and differentiation rates of: 1) sex and age of donors; 2) site of the muscle biopsy; and 3) delay before processing of the muscle biopsy sample. We used a standardized primary muscle cell culture procedure on 206 normal muscle samples obtained from different muscle groups of patients aged from 20 to 88 years, at time of orthopedic surgery. Sex of donors did not influence muscle culture parameters. In contrast, aging tended to affect muscle cell yield (age group 50-59 years vs 70-79 years, P < 0.08), but not myogenic cell abilities to proliferate and to fuse into myotubes. The anatomic origin of muscle samples used for culture appeared to influence culture parameters. In contrast with other tested muscles, the tensor fasciae muscle gave both a good cell yield (174 +/- 25 10(3) cells per gram) and homogeneous proliferation and differentiation rates. Storage of the muscle sample at 4 degrees C in transport medium was associated with a very high cell yield when processing was done in early hours after biopsy (277 +/- 50 10(3) cells/g), a high and stable cell yield when processing was done from day 1 to day 3 after biopsy (185 +/- 15 10(3) cells/g), and a poor cell yield when processing was done after day 4 (111 +/- 13 10(3) cells/g). Storage of muscle biopsy samples at 4 degrees C for 1 to 4 days was associated with good proliferation and fusion rates. In conclusion, these data validate a convenient procedure of primary human muscle cell culture, using tensor fasciae muscle biopsy, which is easily done at time of orthopedic surgery, obtained from men and women of all ages (if possible less than 70 years to obtain good cell yield), and allowing of 1-3 days of storage before processing that may compensate uncertainty of the exact time of availability of muscle samples for the scientist.

Adult↗
PubMed1987

Transformation of contraction speed in muscle following cross-reinnervation; dependence on muscle size.

The characteristics of isometric contractions and the force-velocity relation were studied in flexor digitorum longus, flexor hallucis longus and soleus muscles of the cat, in situ, at 37 degrees C and with nerve stimulation. The two flexors were identified as typical fast twitch muscles and the soleus as a typical slow twitch muscle. Following self-reinnervation, both fast and slow muscles retained, to a large extent, their basic contraction characteristics. The soleus muscle, when cross-reinnervated with the nerve of either flexor hallucis longus muscle or extensor digitorum longus muscle exhibited a more complete slow-to-fast transformation than when cross-reinnervated with the nerve of flexor digitorum longus muscle. The flexor digitorum longus muscle underwent a greater degree of fast-to-slow transformation than the flexor hallucis longus muscle, when each was cross-reinnervated with the soleus nerve. The data previously reported for sarcomere shortening velocities of the cross-reinnervated muscles in the rat, the rabbit and the cat are reviewed in the light of present findings. It is found that the discrepancies obtained between species and between different muscles in the same species, with respect to the degree of muscle-speed transformation following cross-reinnervation, are correlated with the differences in the size-ratio of the muscles used in the cross-reinnervation procedure.

Animals↗
PubMed1997

Muscle transformation of the sartorius muscle in a canine model: clinical impact for electrodynamic graciloplasty as a "neosphincter".

PURPOSE: Transformation of fast-twitching skeletal muscles to slow-twitching, slowly fatigable muscles has become of clinical interest in the recent past. Transposition and transformation of the gracilis muscle to use it as a substitute for a resected or defected anal sphincter (graciloplasty) have been reported as achieving promising results in the treatment of fecal incontinence caused by sphincter defects or following abdominoperineal anorectal excision for cancer. METHOD: This experimental study used a canine model and the sartorius muscle to evaluate the functional efficiency of two different configurations of the muscle loop to compare the presently applied transformation program (8 weeks) with a shorter (5 weeks) protocol. In six beagle dogs, both sartorius muscles were wrapped around two stomas, either in an alpha fashion or in the so-called split-sling technique. Muscle transformation was achieved by controlled neuromuscular stimulation either during eight (Program A) or five weeks (Program B). After completion of the transformation period, the function of the muscle slings was evaluated by manometry, and histomorphologic evaluation of the sartorius muscles was performed. RESULTS: It was shown that muscle transformation led to a slowly fatigable muscle that made it possible to perform continuos (tetanic) contraction, regardless of the configuration or the duration of the transformation. Median pressures created by these muscles also did not differ significantly. In accordance with these functional findings, the histologic evaluation showed the typical, significant increase of Type I fibers in both muscle slings and following both transformation protocols. Although the decrease of fast-twitching Type II fibers was more pronounced following the conventional (8 weeks) program, this finding did not influence the functional results. CONCLUSIONS: Results of our experiment indicate the possibility for using a shorter transformation protocol for transformation of the gracilis muscle during graciloplasty in the clinical setting. Furthermore, the efficacy and safety of the modified (split-sling) wrap technique was demonstrated.

Anal Canal↗
PubMed2001

Differential catabolism of muscle protein in garden warblers (Sylvia borin): flight and leg muscle act as a protein source during long-distance migration.

Samples of flight and leg muscle tissue were taken from migratory garden warblers at three different stages of migration: (1) pre-flight: when birds face an extended flight phase within the next few days, (2) post-flight: when they have just completed an extended flight phase, and (3) recovery: when they are at the end of a stop-over period following an extended flight phase. The changes in body mass are closely related to the changes in flight (P<0.001) and leg muscle mass (P<0.001), suggesting that the skeletal muscles are involved in the protein metabolism associated with migratory flight. From pre- to post-flight, the flight and the leg muscle masses decrease by about 22%, but are restored to about 12% above the pre-flight masses during the recovery period. Biochemical analyses show that following flight a selective reduction occurred in the myofibrillar (contractile) component of the flight muscle (P<0.01). As this selective reduction accounts only for a minor part of the muscle mass changes, sarcoplasmic (non-contractile) and myofibrillar proteins of both the flight and leg muscle act as a protein source during long-distance migration. As a loss of leg muscle mass is additionally observed besides the loss in flight muscle mass, mass change seems not to be strictly associated with the mechanical power output requirements during flight. Whereas the specific content of sarcoplasmic proteins in the flight muscle is nearly twice as high as that in the leg muscle (P<0.001), the specific content of myofibrillar proteins differs only slightly (P < 0.05), being comparably low in both muscles. The ratio of non-contractile to contractile proteins in the flight muscle is one of the highest observed in muscles of a vertebrate.

Adipose Tissue↗
PubMed2000

Ultrastructural analysis of the transdifferentiation of smooth muscle to skeletal muscle in the murine esophagus.

The ultrastructure of the mouse esophagus at the level of the diaphragm was studied from embryo day 17 to adult. The transdifferentiation of smooth muscle into skeletal muscle was categorized into seven ultrastructural stages: during phase I normal smooth muscle myogenesis was observed. In phase II subpopulations of cells changed into aggregates of myoblast-like cells. At the center of these cell aggregates, phase III cells appeared that contained condensed myofilaments. Dense bodies and dense bands appeared enlarged by the accumulation of thin filaments. In phase IV the condensed myofilaments organized into sarcomere pretemplate structures. The dense bodies and dense bands formed rudimentary Z-lines. In phase V the sarcomere templates appeared as more defined structures and began to align. An elaborate perinuclear region appeared. During phase VI, skeletal muscle sarcomeres were apparent and myofilaments were arranged in a typical hexagonal array. Phase VII skeletal muscle fibers were unique with sarcomeric bifurcations and anastomoses between adjacent myofibrils. Non-contractile organelles were less organized in these cells than in skeletal muscles such as rectus and vastus lateralis muscles. During the transdifferentiation process, other cell types remained unchanged, except the number of interstitial cells of Cajal became reduced. Immunocytochemical studies with antibodies against smooth and skeletal muscle myosin were also performed during the process of transdifferentiation. An osmium tetroxide/potassium ferricyanide en bloc mordant enabled the use of ultrathin Unicryl sections for immunocytochemistry. Cells exhibited smooth muscle myosin-like immunoreactivity from the smooth muscle stage through the condensed myofilament stage. Cells were immunopositive for skeletal muscle myosin before the formation of sarcomere templates, during the condensed stage, and after development of mature skeletal muscle cells. We also observed a hybrid muscle cell with properties of both smooth and skeletal muscle cells.

Actin Cytoskeleton↗
PubMed1984

Crossed and uncrossed central effects of muscle spindle afferents from the lateral pterygoid muscle of the guinea pig.

Physiological evidence is presented for the presence of stretch reflexes in the lateral pterygoid (Pt) muscle of the guinea pig. The central reflex effects of excitation of Pt stretch reflex afferents were also investigated. Passive lateral jaw displacement, which resulted in stretch of the Pt muscle on the side of jaw movement and stretch of the zygomatico-mandibularis (Z) muscle on the side contralateral to the movement, evoked increased EMG activity in these muscles. Stimulation of the trigeminal mesencephalic nucleus (mes V) evoked monosynaptic reflexes in both the Pt and Z nerves. Tonic stretch of the Pt muscle facilitated the monosynaptic reflex in the Pt nerve evoked by stimulation of mes V. Tonic vibration of the Pt muscle facilitated the mes V evoked monosynaptic reflex in the nerves to the ipsilateral Pt and contralateral Z muscles. Conversely, tonic vibration of the Z muscle facilitated the monosynaptic reflex evolved by mes V stimulation in the contralateral Pt and ipsilateral Z nerve. The results support the view that muscle spindles exist in the Pt and Z muscles and that there is a monosynaptic stretch reflex for both the Pt and Z muscles with cell bodies located in the mes V nucleus. It was also shown that the ipsilateral Pt muscle and the contralateral Z muscle act as synergists in the production of lateral jaw movements and that the organization of the stretch reflexes originating from the Pt and Z muscles support their synergistic action.

Animals↗
PubMed2004

Robust conversion of marrow cells to skeletal muscle with formation of marrow-derived muscle cell colonies: a multifactorial process.

OBJECTIVE: Murine marrow cells are capable of repopulating skeletal muscle fibers. A point of concern has been the "robustness" of such conversions. We have investigated the impact of type of cell delivery, muscle injury, nature of delivered cell, and stem cell mobilizations on marrow-to-muscle conversion. METHODS: We transplanted green fluorescence protein (GFP)-transgenic marrow into irradiated C57BL/6 mice and then injured anterior tibialis muscle by cardiotoxin. One month after injury, sections were analyzed by standard and deconvolutional microscopy for expression of muscle and hematopoietic markers. RESULTS: Irradiation was essential to conversion, although whether by injury or induction of chimerism is not clear. Cardiotoxin- and, to a lesser extent, PBS-injected muscles showed significant number of GFP(+) muscle fibers, while uninjected muscles showed only rare GFP(+) cells. Marrow conversion to muscle was increased by two cycles of G-CSF mobilization and to a lesser extent by G-CSF and steel or GM-CSF. Transplantation of female GFP to male C57BL/6 and GFP to ROSA26 mice showed fusion of donor cells to recipient muscle. High numbers of donor-derived muscle colonies and up to 12% GFP(+) muscle cells were seen after mobilization or direct injection. These levels of donor muscle chimerism approach levels that could be clinically significant in developing strategies for the treatment of muscular dystrophies. CONCLUSION: In summary, the conversion of marrow to skeletal muscle cells is based on cell fusion and is critically dependent on injury. This conversion is also numerically significant and increases with mobilization.

Animals↗
PubMed2004

Reperfusion injury to skeletal muscle affects primarily type II muscle fibers.

INTRODUCTION: The injury caused by reperfusion of ischemic skeletal muscle is mediated by the membrane attack complex of complement (C) . This C activation results from local classical pathway activation after deposition of IgM in injured muscle, an event analogous to C deposition in the mucosa of the gut during reperfusion . Our past analysis has indicated that the injury is not uniform even within a single microscopic section. This study was performed to elucidate the exact site of IgM and C deposition on muscle injured by ischemia and reperfusion. MATERIALS AND METHODS: C57Bl/6 mice were subjected to 2 h of tourniquet-induced hindlimb ischemia followed by reperfusion for 0-6 h. Three muscle groups (vastus, gastrocnemius, and soleus) of varying fast-myosin content were compared for muscle fiber damage and C deposition. Adjacent paraffin-embedded cross-sections were immunostained to correlate C3 deposition with muscle fiber type as defined by monoclonal antibodies. RESULTS: Muscle injury after ischemia and reperfusion is not uniform and not all fibers in the same microscopic field are affected. Damaged fibers are also those to which IgM and C bind. Immunostaining for slow-twitch (Type 1) or fast-twitch (Type 2) fibers reveals that injury and C3 deposition is confined to Type 2 fibers with lower myosin content. A correlation of Type 2 fiber content and degree of muscle injury showed that the predominantly fast-twitch vastus muscle had the greatest number of damaged fibers per x10 field (28.2 +/- 12.4) when compared to the mixed fiber-type gastrocnemius muscle (20.5 +/- 5.3) and the mixed, but slow-twitch enriched soleus muscle (17.3 +/- 11.8). CONCLUSION: Complement activation and skeletal muscle reperfusion injury occurs predominantly on Type 2 fibers with low myosin content. This suggests that attempts to control the post-reperfusion inflammation will likely produce substantial muscle recovery. Furthermore, the basis of IgM deposition and complement activation may be revealed in the comparison of the two muscle fiber types.

Animals↗
PubMed2005

The staircase phenomenon at the corrugator supercilii muscle in comparison with the hand muscles.

BACKGROUND: Phonomyography (PMG) is a novel method to monitor neuromuscular block. It is non-invasive and can be applied to any muscle. It can be used interchangeably with mechanomyography (MMG). The staircase phenomenon has not been investigated for this method or at the corrugator supercilii muscle. The purpose of this work was to determine the staircase effect at three different muscles using two different methods. METHODS: In 10 patients undergoing general anaesthesia with sevoflurane, using a laryngeal mask airway without the aid of neuromuscular block, one piezo-electric microphone each was applied to the corrugator supercilii muscle and the first dorsal interosseus muscle. In addition, a force transducer was attached to the tip of the thumb to determine the force of the adductor pollicis muscle. Supramaximal stimulation at 1 Hz was used at the ulnar and the facial nerve. All signals were simultaneously recorded for 30 min. Data are presented as means (SD). RESULTS: The staircase effect was significantly positive for the first dorsal interosseus muscle and the adductor pollicis muscle. The signal potentiation was not significantly different between the first dorsal interosseus muscle with a maximum increase at 148 (19)% using PMG, and the adductor pollicis muscle at 154 (22)% using MMG. The evoked signals reached a plateau after 15-18 min at both muscles. There was only a small initial increase in signal height at the corrugator supercilii to a maximum of 117 (20)% at 7 min, after which the signals decreased to reach a plateau at 25 min. In comparison with the signal height of 105 (25)% at 30 min, there was no significant difference of signal heights throughout the observation period. CONCLUSIONS: A positive staircase phenomenon is found equally at the first dorsal interosseus muscle and the adductor pollicis muscle. There is no significant staircase effect at the corrugator supercilii muscle.

Acoustics↗
PubMed2001

Specific force deficit in skeletal muscles of old rats is partially explained by the existence of denervated muscle fibers.

We tested the hypothesis that denervated muscle fibers account for part of the specific force (sF(o)) deficit observed in muscles from old adult (OA) mammals. Whole muscle force (F(o)) was quantified for extensor digitorum longus (EDL) muscles of OA and young adult (YA) rats. EDL muscle sF(o) was calculated by dividing F(o) by either total muscle fiber cross-sectional area (CSA) or by innervated fiber CSA. Innervated fiber CSA was estimated from EDL muscle cross sections labeled for neural cell adhesion molecules, whose presence is a marker for muscle fiber denervation. EDL muscles from OA rats contained significantly more denervated fibers than muscles from YA rats (5.6% vs 1.1% of total CSA). When compared with YA muscle, OA muscle demonstrated deficits of 34.1% for F(o), 28.3% for sF(o), and 24.9% for sF(o) calculated by using innervated CSA as the denominator. Denervated muscle fibers accounted for 11.3% of the specific force difference between normal YA and OA skeletal muscle. Other mechanisms in addition to denervation account for the majority of the sF(o) deficit with aging.

Aging↗
PubMed2002

Stretching of the Mueller muscle results in involuntary contraction of the levator muscle.

PURPOSE: Since the levator muscle involuntarily and tonically contracts against the weight and elastic resistance of the upper eyelid to maintain an adequate visual field, a mechanoreceptor such as a muscle spindle or a periodontal mechanoreceptor is thought to be essential for its functioning. It was surmised that the Mueller muscle might act as a serial kind of muscle spindle of the levator muscle. METHODS: The response of the bilateral levator muscles evoked by stretching the Mueller muscle of each eyelid of 87 patients with dermatochalasis or aponeurotic blepharoptosis was electromyographically and photographically recorded. RESULTS: Stretching of the unilateral Mueller muscle evoked contraction of the ipsilateral levator muscle in 18 and of the bilateral levator muscle in 69 of the 87 patients. CONCLUSIONS: The Mueller muscle can be thought of as a large, serial kind of muscle spindle, so that stretching by voluntary phasic contraction of the levator muscle for initial eye opening may evoke an afferent impulse to the mesencephalic trigeminal nucleus. Subsequently, this nucleus may stimulate the central caudal nucleus of the oculomotor nuclear complex, leading to involuntary tonic contraction of the ipsilateral or bilateral levator muscles, in the form of a continuous stretch reflex, to maintain an adequate visual field.

Adult↗
PubMed2006

An allometric analysis of the number of muscle spindles in mammalian skeletal muscles.

An allometric analysis of the number of muscle spindles in relation to muscle mass in mammalian (mouse, rat, guinea-pig, cat, human) skeletal muscles is presented. It is shown that the trend to increasing number as muscle mass increases follows an isometric (length) relationship between species, whereas within a species, at least for the only essentially complete sample (human), the number of spindles scales, on average, with the square root rather than the cube root of muscle mass. An attempt is made to reconcile these apparently discrepant relationships. Use of the widely accepted spindle density (number of spindles g(-1) of muscle) as a measure of relative abundance of spindles in different muscles is shown to be grossly misleading. It is replaced with the residuals of the linear regression of ln spindle number against ln muscle mass. Significant differences in relative spindle abundance as measured by residuals were found between regional groups of muscles: the greatest abundance is in axial muscles, including those concerned with head position, whereas the least is in muscles of the shoulder girdle. No differences were found between large and small muscles operating in parallel, or between antigravity and non-antigravity muscles. For proximal vs. distal muscles, spindles were significantly less abundant in the hand than the arm, but there was no difference between the foot and the leg.

Adult↗
PubMed1982

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

1. Discharges have been recorded from afferents of the soleus muscle following reinnervation by the nerve of a fast twitch muscle, extensor digitorum longus. Recordings were made 227-449 d post-operatively.2. The gross afferent discharge from the cross-reinnervated soleus suggested the presence of fewer mechanosensitive receptors than in normal muscles, as judged by discharges seen during a maximal muscle twitch.3. A comparison of receptors in the cross-reinnervated muscle with afferents from a self-reinnervated muscle showed that many of the responses in the self-reinnervated muscle were also abnormal. It was concluded that much of the disruption resulted from the surgical interference and that rather less could be attributed to the foreign nerve.4. A detailed analysis of response characteristics of receptors in cross-reinnervated soleus muscles of five cats showed that afferent conduction velocities of identified spindles and tendon organs were generally lower than normal and responses to muscle stretch or vibration were often atypical. A large number of afferents which could not be classified as muscle spindles or tendon organs included a group called contraction receptors. These responded generally only during maximal muscle contractions and with a rather feeble discharge. A second group consisted of afferents in which impulses could be elicited by electrical stimulation of the nerve but not by any mechanical activity in the muscle.5. In a further five animals a detailed study was made of the motor supply of muscle spindles. A fusimotor innervation was common, but invariably stimulation of the gamma fibre had a static action on the spindle. No purely dynamic fusimotor fibres were encountered. There were many static beta fibres (skeletofusimotor) no dynamic betas and three axons conducting in the alpha range, which developed no tension, yet produced specific intrafusal effects. Two of these had a mixed static-dynamic action while the third was purely static.6. It was concluded that in the cross-reinnervated soleus muscle the majority of afferents were abnormal in one or other respect. The central action of such abnormal receptors would have to be taken into account when seeking explanations of the transformation of a muscle's mechanical properties following reinnervation by a foreign nerve.

Action Potentials↗
PubMed2006

Expression of slow myosin heavy chain during muscle regeneration is not always dependent on muscle innervation and calcineurin phosphatase activity.

In the literature, there is an ambiguity as to the respective roles played by calcineurin phosphatase activity (CPA) and muscle innervation in the reestablishment of the slow-twitch muscle phenotype after muscle regeneration in different species. In this study, we wanted to determine the role of calcineurin and muscle innervation on the appearance and maintenance of the slow phenotype during mouse muscle regeneration. The pattern of myosin expression and CPA was analyzed in adult (n=15), regenerating (n=45) and denervated-regenerating (n=32) slow-twitch soleus and fast-twitch extensor digitorum longus (EDL) muscles. Moreover, in a second group of denervated-regenerating mice (n=9), the animals were treated with a calcineurin inhibitor. Regeneration was induced by injection of cardiotoxin and in the denervated-regenerating group, denervation was carried out by cutting the sciatic nerve before the administration of cardiotoxin. In innervated-regenerating soleus muscle, CPA increased continuously after 10 days postinjury and by 21 days, there was a 3.5-fold increase in CPA compared with adult basal level, whereas in innervated-regenerating EDL muscle, CPA remained unchanged. Moreover, our results show that in denervated-regenerating muscles, the MyHC profile was identical in spite of the functional differences inherent in these muscles. In long-term denervated-regenerating muscles, a slow muscle phenotype was reexpressed both in the presence or absence of calcineurin inhibitor. Our results show that although in innervated-regenerating mouse muscle, the appearance of a slow phenotype is correlated with a peak of CPA, in denervated-regenerating muscles, a slow phenotype is triggered and maintained in a calcineurin- and nerve-independent manner.

Animals↗
PubMed2000

The zebrafish slow-muscle-omitted gene product is required for Hedgehog signal transduction and the development of slow muscle identity.

Hedgehog proteins mediate many of the inductive interactions that determine cell fate during embryonic development. Hedgehog signaling has been shown to regulate slow muscle fiber type development. We report here that mutations in the zebrafish slow-muscle-omitted (smu) gene disrupt many developmental processes involving Hedgehog signaling. smu(-/-) embryos have a 99% reduction in the number of slow muscle fibers and a complete loss of Engrailed-expressing muscle pioneers. In addition, mutant embryos have partial cyclopia, and defects in jaw cartilage, circulation and fin growth. The smu(-/-) phenotype is phenocopied by treatment of wild-type embryos with forskolin, which inhibits the response of cells to Hedgehog signaling by indirect activation of cAMP-dependent protein kinase (PKA). Overexpression of Sonic hedgehog (Shh) or dominant negative PKA (dnPKA) in wild-type embryos causes all somitic cells to develop into slow muscle fibers. Overexpression of Shh does not rescue slow muscle fiber development in smu(-/-) embryos, whereas overexpression of dnPKA does. Cell transplantation experiments confirm that smu function is required cell-autonomously within the muscle precursors: wild-type muscle cells rescue slow muscle fiber development in smu(-/-) embryos, whereas mutant muscle cells cannot develop into slow muscle fibers in wild-type embryos. Slow muscle fiber development in smu mutant embryos is also rescued by expression of rat Smoothened. Therefore, Hedgehog signaling through Slow-muscle-omitted is necessary for slow muscle fiber type development. We propose that smu encodes a vital component in the Hedgehog response pathway.

Animals↗