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Spontaneous muscle action potentials are blocked by N-type and P/Q-calcium channels blockers in the rat spinal cord-muscle co-culture system.

This study investigated the effects of the calcium channel blockers nicardipine, calcicludine, omega-conotoxin GVIA, omega-agatoxin IVA, SNX-482, and NiCl on spontaneous muscle action potential of a rat spinal cord-muscle co-culture system. Spontaneous muscle action potential of the innervated muscle cells was blocked by d-tubocurarine (1 microM), but was not significantly affected by the L-type channel blocker nicardipine (100 nM). The neuronal L-type calcium channel blocker, calcicludine (50 and 100 nM), also had no effect on the frequency of spontaneous muscle action potential. However, nicardipine (100 nM) and calcicludine (100 nM) significantly increased the amplitude of muscle action potential. Application of the N-type calcium channel blocker, omega-conotoxin GVIA (50 and 100 nM), and the P/Q-type calcium channel blocker, omega-agatoxin IVA (10, 30, 50, and 100 nM), blocked the frequency and amplitude of spontaneous muscle action potential of the spinal cord-muscle co-cultured cells. In contrast, spontaneous muscle action potential was not affected by the R-type calcium channel blockers SNX-482 (100 nM) or NiCl (500 nM). These results indicate that blockers of N- and P/Q-type voltage-dependent calcium channels inhibit transmitter release at neuromuscular junctions in the rat spinal cord-muscle co-culture system.

Action Potentials↗

Muscle activity onset in the lumbar multifidus muscle recorded simultaneously by ultrasound imaging and intramuscular electromyography.

BACKGROUND: Delayed anticipatory muscle activity response in deep abdominal and back muscles has been observed in patients with low back pain, indicative of a pathological condition. Muscle activity onset is traditionally recorded by intramuscular electromyography, but there is a need for a non-invasive and less cumbersome recording method in large clinical studies. An experimental study was carried out to explore whether high-frame rate m-mode ultrasound could measure anticipatory muscle responses ("onset") in the lumbar multifidus muscle reliably and comparably accurate to intramuscular electromyography. METHODS: Muscle activity onset was recorded by ultrasound m-mode and intramuscular electromyography. Ultrasound m-mode with a temporal resolution of 500 s(-1) (frames per second) was used to record rapid movements caused by muscle deformations in multifidus. In ultrasound m-mode, the frequency of each echo signal from 0.15 mm incremental depth levels is analysed. The frequency of these signals is proportional to the velocity of the interrogated tissue. The mean amplitude of the high-pass filtered echo signals within a pre-set depth range was plotted against time, and used to indicate onset. The results were compared to muscle activity onset in the multifidus recorded simultaneously by intramuscular electromyography. FINDINGS: High inter-rater agreement was found for visual determination of onset within both methods. The smallest detectable difference was 21 and 24 ms for electromyography and the ultrasound methods, respectively. The ultrasound m-mode method recorded muscle activity onset in the deep multifidus on average 16 ms (SD 21) later than intramuscular electromyography. For single trials, large variation and thus unacceptable method agreement was found. INTERPRETATION: Ultrasound m-mode imaging at high time resolution can detect onset of muscle activity comparably accurate to intramuscular electromyography, but with a small systematic delay that should be corrected for in onset determination by m-mode ultrasound. Regardless of recording method, onset estimates should be based on averaged values of repeated trials. Further studies are needed to explore the applicability of the ultrasound method in clinical settings.

Adult↗

Early development of EMG localized muscle fatigue in hand muscles of patients with chronic heart failure.

BACKGROUND: Patients with chronic heart failure (CHF) frequently complain of fatigue and exercise intolerance that are not directly related to the severity of cardiac failure. A not well-defined muscle function impairment is generally considered the cause of such symptoms. The frequency compression of electromyographic (EMG) signal power spectrum during isometric contractions is commonly accepted as an index of the fatigue occurring in the muscle (localized muscle fatigue). PURPOSE AND METHODS: The purpose of the study was to evaluate muscle fatigue development in a selected group of CHF patients by studying the compression of the EMG signal power spectrum. The first dorsal interosseus of the right, dominant hand was investigated at two levels of contraction: 40% and 80% of the maximal voluntary contraction (MVC). RESULTS: In CHF patients there was early development of localized muscle fatigue during the high level of contraction (80% of MVC). CONCLUSION: This study demonstrates the presence of an early development of localized muscle fatigue in CHF patients and confirms the possibility of an increased glycolytic metabolism. Moreover, the changes seem to show that muscle impairment is not limited to large muscles, but also occurs in small muscles of the hands, frequently used during daily activities. Finally, this study confirms the validity of EMG spectral analysis techniques in evaluating muscle fatigue of CHF patients, suggesting a possible use in the rehabilitation of such patients when the technique is correctly used.

Adult↗

Biliary cirrhosis induces type IIx/b fiber atrophy in rat diaphragm and skeletal muscle, and decreases IGF-I mRNA in the liver but not in muscle.

BACKGROUND/AIMS: Patients with cirrhosis complain of fatigue, which in part may be due to the progressive muscle atrophy, noted especially when signs of decompensation appear. In addition, weaning from mechanical ventilation may be difficult in some patients following liver transplantation. Since little is known about the peripheral muscles and the diaphragm in cirrhosis, we investigated diaphragm and gastrocnemius histochemical properties, and diaphragm contractile properties in male rats with biliary cirrhosis. In addition, the extent to which insulin-like growth factor I (IGF-I) was involved in the regulation of muscle function was also examined, since IGF-I is known to induce growth and regeneration as well as to exert a protein anabolic action. METHODS: Ten rats underwent a sham operation, while another ten underwent bile duct ligation and excision. After 5 weeks, biliary cirrhosis was confirmed histologically in random liver biopsies. RESULTS: Compared to sham animals, diaphragm mass in cirrhotic rats was decreased by 10% (p<0.05), while masses of other respiratory (e.g. scalenus medius -21%, p<0.001) or peripheral muscles (e.g. gastrocnemius -24%, p<0.0001) decreased more. No changes in diaphragm force nor in its endurance were observed between the two groups. However, a clear decrease in the cross-sectional area of type IIx/b muscle fiber was present in both diaphragm (1360+/-147 vs 1112+/-167 microm2, p<0.02) and gastrocnemius (1954+/-265 vs 2328+/-245 microm2, p<0.02). Finally, hybridization of Northern blot with a rat cDNA IGF-I probe (gift from Dr D. Leroith, Bethesda, USA) labeled with alpha-32P revealed that in cirrhotic rats, the relative expression of IGF-I was markedly reduced by 45% in the liver (p<0.05) but was unchanged in the two muscles studied. CONCLUSIONS: In this model of biliary cirrhosis: (i) muscle wasting was less pronounced in the diaphragm than in other muscles; (ii) type IIx/b fiber atrophy in respiratory (diaphragm) and peripheral muscles (gastrocnemius) developed while diaphragm contractile properties remained unchanged; and (iii) the relative expression of IGF-I was reduced in the liver only, while it remained unchanged in the muscle. The functional significance of these changes, their pathogenesis and presence in other models and in human cirrhosis remain to be elucidated.

Animals↗

Mechanical simulation of muscle loading on the proximal femur: analysis of cemented femoral component migration with and without muscle loading.

OBJECTIVE: This study examines the effect of including muscle forces in fatigue tests of cemented total hip arthroplasty reconstructions. DESIGN: An experimental device capable of applying the joint reaction force, the abductor force, the vastus lateralis force, and the tensor fasciae latae force to the implanted femur is described. BACKGROUND: Current in vitro fatigue tests of cemented total hip arthroplasty reconstructions do not apply physiological muscle loads. Experimental and numerical studies report significant differences in stresses obtained in the cement mantle depending on the loads applied. The differing stresses may alter the outcome of an in vitro test. METHODS: Ten femoral components were reproducibly implanted into proximal composite femurs. Five of these femoral components were tested using a loadprofile which included muscle loading, five were tested without muscle loading. The migration of each femoral component was monitored continuously during dynamic fatigue tests. RESULTS: Clinically comparable migration amounts were found for both sets of femoral components, with the femoral components tested with muscle loading experiencing lower mean migration, lower mean inducible displacement, and less experimental scatter. CONCLUSIONS: The inclusion of muscle forces seems to stabilise the femoral component during the test. In vitro fatigue tests of cemented total hip arthroplasty reconstructions should include muscle loading to provide increased confidence in the results obtained. RELEVANCE: This study examines how the migration of cemented femoral hip prostheses is influenced by muscle forces. Hip prostheses are one of the few medical devices for which pre-clinical testing protocols have emerged, and this study ascertains whether or not the inclusion of muscle forces is necessary for pre-clinical tests. The conclusion that muscle loading should be included, and that it is important for the development of a new generation of standardised tests to provide enhanced patient protection against functionally poor prostheses.

Arthroplasty, Replacement, Hip↗

Effects of abdominal belts on intra-abdominal pressure, intra-muscular pressure in the erector spinae muscles and myoelectrical activities of trunk muscles.

OBJECTIVE: To evaluate the effects of abdominal belts on lifting performance, muscle activation, intra-abdominal pressure and intra-muscular pressure of the erector spinae muscles. DESIGN: Simultaneous measurement of intra-abdominal pressure, intra-muscular pressure of the erector spinae muscles was performed during the Valsalva maneuver and some isometric lift exertions. BACKGROUND: While several hypotheses have been suggested regarding the biomechanics of belts and performance has been found to increase when lifting with belts, very little is known about the modulating effects on trunk stiffness. At present, there is no reason to believe that spine tolerance to loads increases with belts. METHODS: An abdominal belt designed for weightlifting was used. Intra-abdominal pressure, intra-muscular pressure of the erector spinae muscles and myoelectric activities of trunk muscles (erector spinae, rectus abdominis and external oblique) were measured simultaneously during the Valsalva maneuver as well as three types of isometric lifting exertions (arm, leg and torso lift). A paired t-test was used to analyze for statistical differences between the two conditions (without-belt and with-belt) in intra-abdominal pressure, intra-muscular pressure of the erector spinae muscles and in the integrated EMG of the trunk muscles. RESULTS: Intra-muscular pressure of the erector spinae muscles increased significantly by wearing the abdominal belt during Valsalva maneuvers and during maximum isometric lifting exertions, while maximum isometric lifting capacity and peak intra-abdominal pressure were not affected. Integrated EMG of rectus abdominis increased significantly by wearing the abdominal belt during Valsalva maneuvers (after full inspiration) and during isometric leg lifting. CONCLUSIONS: Wearing abdominal belts raises intra-muscular pressure of the erector spinae muscles and appears to stiffen the trunk. Assuming that increased intra-muscular pressure of the erector spinae muscles stabilizes the lumbar spine, wearing abdominal belts may contribute to the stabilization during lifting exertions.

Abdominal Muscles↗

Postural sway under muscle vibration and muscle fatigue in humans.

Separate studies have demonstrated that vibration and fatigue of ankle muscles alter postural control. The purpose of the present experiment was to investigate the effect of ankle muscle vibration on the regulation of postural sway in bipedal stance following ankle muscle fatigue. Center of foot pressure displacements were recorded using a force platform. Results showed a similar increase in postural sway under muscle fatigue as well as under muscle vibration. Interestingly, under muscle fatigue muscle vibration did not induce a further increase in postural sway. Two hypotheses could, at least, account for this observation: (1). fatigued muscles are less sensitive to muscle vibration and (2). the central nervous system relies less upon proprioceptive information originating from fatigued muscles for regulating postural sway.

Adult↗

Staining of human thyroarytenoid muscle with myosin antibodies reveals some unique extrafusal fibers, but no muscle spindles.

This study describes the myosin composition of extrafusal and intrafusal muscle fibers found in the human thyroarytenoid (TA) and sternohyoid (control) muscles. We sought to determine the presence of muscle spindles in the TA muscle, and to identify unusual extrafusal fiber types, using the commonly accepted approach of tissue staining with myosin isoform specific antibodies. Extrafusal fibers are organized into motor units, which subsequently produce muscle movement, whereas intrafusal fibers compose muscle spindles, the primary stretch receptor that provides afferent (feed back) information to the nervous system for regulation of motor unit length and tonicity. Immunohistochemical identification of muscle spindles was confirmed in sternohyoid, but not in TA samples; however, some extrafusal fibers contained tonic myosin. These results indicate that human TA muscle functions similar to some mammalian extraocular muscle, performing unloaded (non-weight bearing) contractions without afferent information from native muscle spindles.

Aged↗

Neonatal arthrogryposis and absent limb muscles: a muscle developmental gene defect?

We describe a child who presented at birth with arthrogryposis. Following a muscle biopsy a diagnosis of congenital muscular dystrophy was made and a skin biopsy 12 years later confirmed the presence of merosin. Her clinical picture was unusual, however, for merosin-positive congenital muscular dystrophy. She had extreme wasting and weakness of her arms and legs. In contrast, she had good neck and trunk control, and no facial or respiratory muscle weakness. We have used magnetic resonance imaging to examine the pattern of muscle involvement in this case. No recognizable muscle could be identified in the limbs. In contrast, the axial muscles were preserved. This striking pattern of virtual absence of muscles in the limbs with sparing of the axial muscle suggests that a gene responsible for the migration and/or proliferation of limb muscle precursor cells may be involved in the disease process. It is recognized that merosin-positive congenital muscular dystrophy is a heterogeneous disease. Magnetic resonance imaging is a useful tool for examining in detail the pattern of muscle involvement and identifying individual phenotypes. Understanding more about which muscles are affected in children with congenital myopathies may provide information on the underlying pathological process and help in the search for candidate proteins and genes.

Arthrogryposis↗

Comparison of sarcoplasmic reticulum capabilities in toadfish (Opsanus tau) sonic muscle and rat fast twitch muscle.

The sonic muscle of the oyster toadfish, Opsanus tau, can produce unfused contractions at 300 Hz. Electron microscopy shows a great abundance of the Sarcoplasmic reticulum (SR) in this muscle, but no functional characterization of the capabilities of the SR has been reported. We measured the oxalate-supported Ca2+ uptake rate and capacities of homogenates of toadfish sonic muscle and rat extensor digitorum longus (EDL) muscle, and estimated the number of pump units by titration with thapsigargin, a high-affinity, specific inhibitor of the SR Ca-ATPase. The Ca2+ uptake rate averaged 70.9 +/- 9.5 mumol min -1 per g tissue for the toad fish sonic muscle, and 73.5 +/- 3.7 mumol min -1 g-1 for rat EDL. The capacity for Ca2+ -oxalate uptake was 161 +/- 20 mumol g -1 and 33 +/- 2 mumol g -1 for toadfish sonic muscle and rat EDL, respectively. Thus, the rates of Ca2+ uptake were similar in the two muscles, but the toadfish sonic muscle had about five times the capacity of the rat EDL. The number of pumps as estimated by thapsigargin titration was 68 +/- 4 nmol of Ca-ATPase per g tissue in the toadfish, and 42 +/- 5 nmol Ca-ATPase per g tissue in the rat EDL. The turnover number, defined as the Ca2+ uptake divided by the number of pumps, was 1065 +/- 150 min -1 for toadfish and 1786 +/- 230 min -1 for rat EDL (p < 0.05) at 37 degrees C. The Ca2+ uptake rate of toadfish sonic muscle at 22 degree C, a typical temperature for calling toadfish, averaged 42 +/- 1% of its rate at 37 degree C. At these operating temperatures, the toadfish SR is likely to be slower than the rat fast-twitch SR, yet the toadfish sonic muscle supports more rapid contractions. One explanation for this is that the voluminous SR provides activator Ca2+ for contraction, but the abundant parvalbumin plays a major role in relaxation.

Animals↗

Effects of respiratory muscle training and electrical stimulation of abdominal muscles on respiratory capabilities in tetraplegic patients.

Thirteen tetraplegic patients were included in the study of the effects of respiratory muscle training and of electrical stimulation of the abdominal muscles on their respiratory capabilities. Each patient was subjected for three 1 month lasting periods of the study: for inspiratory muscle training, expiratory muscle training and for a period without training. The sequence of these three periods was random for each patient. Respiratory tests (RT) measuring forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were conducted before and following each monthly period. Measurements were taken under four sets of conditions: the patients' unassisted efforts, their efforts combined with pressure manually applied by a therapist to the upper part of their abdomen, and their efforts accompanied by electrical stimulation (ES) of the abdominal muscles during the early phase of expirium, once triggered by the therapist and once by the patients themselves. RT values were increasing following respiratory muscle training and inspiratory training apparently had a slightly greater effect than its expiratory counterpart. The increments of values of RT were statistically significant (P < 0.05) after the inspiratory muscle training. RT measurements were greater when the patient's voluntary effort was combined with ES of abdominal muscles than when it was not. This study concludes that respiratory muscle training is a potentially effective approach and that ES of the abdominal muscles has potentials to improve coughing in tetraplegic patients.

Abdominal Muscles↗

Neural regulation of the formation of skeletal muscle phosphorylase kinase holoenzyme in adult and developing rat muscle.

Neural influences on the co-ordination of expression of the multiple subunits of skeletal muscle phosphorylase kinase and their assembly to form the holoenzyme complex, alpha4beta4gamma4delta4, have been examined during denervation and re-innervation of adult skeletal muscle and during neonatal muscle development. Denervation of the tibialis anterior and extensor digitorum longus muscles of the rat hindlimb was associated with a rapid decline in the mRNA for the gamma subunit, and an abrupt decrease in gamma-subunit protein. The levels of the alpha- and beta-subunit proteins in the denervated muscles also declined rapidly, their time course of reduction being similar to that for the gamma-subunit protein, but they did not decrease to the same extent. In contrast with the rapid decline in gamma-subunit mRNA upon denervation, alpha- and beta-subunit mRNAs stayed at control innervated levels for approx. 8-10 days, but then decreased rapidly. Their decline coincided very closely with the onset of re-innervation. Re-innervation of the denervated muscles, which occurs rapidly and uniformly after the sciatic nerve crush injury, produced an eventual slow and prolonged recovery of the mRNA for all three subunits and parallel increases in each of the subunit proteins. A similar co-ordinated increase of both subunit mRNA and subunit proteins of the phosphorylase kinase holoenzyme was observed during neonatal muscle development, during the period when the muscles were attaining their adult pattern of motor activity. The phosphorylase kinase holoenzyme remains in a non-activated form during all of these physiological changes, as is compatible with the presence of the full complement of the regulatory subunits. These data are consistent with a model whereby the transcriptional and translational expression of phosphorylase kinase gamma subunit occurs only with concomitant expression of the alpha and beta subunits. This would ensure that free and unregulated, activated gamma subunit alone, which would give rise to unregulated glycogenolysis, is not produced. The data also suggest that control of phosphorylase kinase subunit expression and the formation of the holoenzyme in skeletal muscle is provided by the motor nerve, probably through imposed levels or patterns of muscle activity.

Aging↗

Muscle afferent inputs to cardiovascular control during isometric exercise vary with muscle group in patients with chronic heart failure.

It is not known whether the contribution of the muscle metaboreflex to the cardiovascular response to isometric exercise varies between different muscles in patients with CHF (chronic heart failure) or whether this depends upon muscle fibre type and training status. To resolve these issues BP (blood pressure) and HR (heart rate) responses were recorded in seven stable CHF patients (ejection fraction 30-40%; age 67+/-3 years) and in six healthy AMA (age-matched active) subjects. The experimental protocol consisted of 2 min of ischaemic isometric exercise at 30% maximum voluntary force, performed in separate trials by the calf plantar flexors (CALF) and handgrip muscles (FOREARM). To isolate the muscle metaboreflex a subsequent period of PECO (post-exercise circulatory occlusion) was performed following exercise. FOREARM and CALF produced similar increases in BP in both the AMA subjects and CHF patients. CHF patients elicited a significantly lower diastolic BP during PECO following CALF in comparison with that following FOREARM (5+/-5 compared with 12+/-3 mmHg respectively). A similar result was seen in AMA subjects. It may be that even the limited weight-bearing locomotor role of the calf muscles constitutes a conditioning stimulus in CHF patients, which leads to desensitization of the muscle metaboreflex, thus producing an attenuated BP elevation. We conclude that it would be incorrect to make general statements about muscle chemoreflex inputs to cardiovascular control in CHF patients based upon measurements made on only one muscle group and without reference to muscle fibre type and training status.

Aged↗

Swelling of sarcoplasmic reticulum in the periphery of muscle fibres after isometric contractions in rat semimembranosus lateralis muscle.

The decline in isometric force, swelling of sarcoplasmic reticulum and loss of desmin was measured in semimembranosus lateralis muscle of male Wistar rats immediately after a short series of brief (500 ms) maximal isometric contractions. For the active muscle, the series ended below (protocol A) and just over muscle optimum length (protocol AA). In one protocol, the muscle remained passive and was extended to lengths just over muscle optimum length (protocol P). After all experimental protocols, no loss of desmin was observed and sarcomere appearance was normal. Protocol A produced swelling (87%) of the sarcoplasmic reticulum but no decline in isometric force. Protocol AA produced larger swelling (147%) of the sarcoplasmic reticulum and an isometric force decline (<49%) at short muscle lengths. Swelling of sarcoplasmic reticulum was observed mainly in the periphery of muscle fibres. Protocol P did not result in swelling of the sarcoplasmic reticulum and isometric force decline. It is concluded that swelling of the sarcoplasmic reticulum in the periphery of muscle fibres after brief maximal isometric contractions is associated with muscle force and not muscle length.

Animals↗

Enzyme activities in the tibialis anterior muscle of young moderately active men and women: relationship with body composition, muscle cross-sectional area and fibre type composition.

The aims of this study were (i) to assess the differences between men and women in maximal activities of selected enzymes of aerobic and anaerobic pathways involved in skeletal muscle energy production, and (ii) to assess the relationships between maximal enzyme activities, body composition, muscle cross-sectional area (CSA) and fibre type composition. Muscle biopsies were obtained from the tibialis anterior (TA) muscle of 15 men and 15 women (age 20-31 years) with comparable physical activity levels. The muscle CSA was determined by magnetic resonance imaging (MRI). Maximal activities of lactate dehydrogenase (LDH), phosphofructokinase (PFK), beta-hydroxyacyl-coenzyme A dehydrogenase (HAD), succinate dehydrogenase (SDH) and citrate synthase (CS), were assayed spectrophotometrically. The proportion, mean area and relative area (proportion x area) of type 1 and type 2 fibres were determined from muscle biopsies prepared for enzyme histochemistry [myofibrillar adenosine triphosphatase (mATPase)]. The men were significantly taller (+6.6%; P < 0.001) and heavier (+19.1%; P < 0.001), had significantly larger muscle CSA (+19.0%; P < 0.001) and significantly larger areas and relative areas of both type 1 and type 2 fibres (+20.5-31.4%; P = 0.007 to P < 0.001). The men had significantly higher maximal enzyme activities than women for LDH (+27.6%; P = 0.007) and PFK (+25.5%; P = 0.003). There were no significant differences between the men and the women in the activities of HAD (+3.6%; ns), CS (+21.1%; P = 0.084) and SDH (+7.6%; ns). There were significant relationships between height and LDH (r = 0.41; P = 0.023), height and PFK (r = 0.41; P = 0.025), weight and LDH (r = 0.45; P = 0.013), and weight and PFK (r = 0.39; P = 0.032). The relationships were significant between the muscle CSA and the activities of LDH (r = 0.61; P < 0.001) and PFK (r = 0.56; P = 0.001), and between the relative area of type 2 fibres and the activities of LDH (r = 0.49; P = 0.006) and PFK (r = 0.42; P = 0.023). There were no significant relationships between HAD, CS and SDH, and height, weight, muscle CSA and fibre type composition, respectively. These data indicate that the higher maximal activities of LDH and PFK in men are related to the height, weight, muscle CSA and the relative area of type 2 fibres, which are all significantly larger in men than women.

3-Hydroxyacyl CoA Dehydrogenases↗

Calcineurin controls nerve activity-dependent specification of slow skeletal muscle fibers but not muscle growth.

Nerve activity can induce long-lasting, transcription-dependent changes in skeletal muscle fibers and thus affect muscle growth and fiber-type specificity. Calcineurin signaling has been implicated in the transcriptional regulation of slow muscle fiber genes in culture, but the functional role of calcineurin in vivo has not been unambiguously demonstrated. Here, we report that the up-regulation of slow myosin heavy chain (MyHC) and a MyHC-slow promoter induced by slow motor neurons in regenerating rat soleus muscle is prevented by the calcineurin inhibitors cyclosporin A (CsA), FK506, and the calcineurin inhibitory protein domain from cain/cabin-1. In contrast, calcineurin inhibitors do not block the increase in fiber size induced by nerve activity in regenerating muscle. The activation of MyHC-slow induced by direct electrostimulation of denervated regenerating muscle with a continuous low frequency impulse pattern is blocked by CsA, showing that calcineurin function in muscle fibers and not in motor neurons is responsible for nerve-dependent specification of slow muscle fibers. Calcineurin is also involved in the maintenance of the slow muscle fiber gene program because in the adult soleus muscle, cain causes a switch from MyHC-slow to fast-type MyHC-2X and MyHC-2B gene expression, and the activity of the MyHC-slow promoter is inhibited by CsA and FK506.

Animals↗

A monoclonal antibody against alpha-smooth muscle actin: a new probe for smooth muscle differentiation.

A monoclonal antibody (anti-alpha sm-1) recognizing exclusively alpha-smooth muscle actin was selected and characterized after immunization of BALB/c mice with the NH2-terminal synthetic decapeptide of alpha-smooth muscle actin coupled to keyhole limpet hemocyanin. Anti-alpha sm-1 helped in distinguishing smooth muscle cells from fibroblasts in mixed cultures such as rat dermal fibroblasts and chicken embryo fibroblasts. In the aortic media, it recognized a hitherto unknown population of cells negative for alpha-smooth muscle actin and for desmin. In 5-d-old rats, this population is about half of the medial cells and becomes only 8 +/- 5% in 6-wk-old animals. In cultures of rat aortic media SMCs, there is a progressive increase of this cell population together with a progressive decrease in the number of alpha-smooth muscle actin-containing stress fibers per cell. Double immunofluorescent studies carried out with anti-alpha sm-1 and anti-desmin antibodies in several organs revealed a heterogeneity of stromal cells. Desmin-negative, alpha-smooth muscle actin-positive cells were found in the rat intestinal muscularis mucosae and in the dermis around hair follicles. Moreover, desmin-positive, alpha-smooth muscle actin-negative cells were identified in the intestinal submucosa, rat testis interstitium, and uterine stroma. alpha-Smooth muscle actin was also found in myoepithelial cells of mammary and salivary glands, which are known to express cytokeratins. Finally, alpha-smooth muscle actin is present in stromal cells of mammary carcinomas, previously considered fibroblastic in nature. Thus, anti-alpha sm-1 antibody appears to be a powerful probe in the study of smooth muscle differentiation in normal and pathological conditions.

Actins↗

Differential neuromuscular effects of vecuronium on the adductor and abductor laryngeal muscles and tibialis anterior muscle in dogs.

We have studied in dogs the neuromuscular blocking effects of vecuronium on the cricothyroid (CT) (a tensor muscle of the vocal folds) and posterior cricoarytenoid (PCA) (sole abductor muscle of the vocal folds) muscles of the larynx and the tibialis anterior (TA) muscle. The lungs of the animals were ventilated mechanically with 0.2% halothane and oxygen. Electromyography (EMG) was performed on the CT, PCA and TA muscles by inserting fine wire electrodes. The evoked compound EMG responses of the three muscles were measured simultaneously in an identical manner by stimulating supramaximally the superior laryngeal, recurrent and sciatic nerves at 0.1 Hz and 0.2 ms. Vecuronium was infused continuously at a rate of 0.01 mg kg-1 min-1 for 8 min. Vecuronium produced more intense neuromuscular block in the CT than in the PCA and TA muscles. The rate of recovery was significantly slowly in the CT compared with the PCA and TA muscles. This study confirms the difference in sensitivity between laryngeal and peripheral muscles, demonstrating that the intrinsic laryngeal muscles do not all behave similarly after administration of vecuronium.

Action Potentials↗