Protein synthesis in adult skeletal muscle after tenotomy: responses to fasting and insulin infusion.

Muscle growth was established in specific muscles in the hindlimb of adult female rats by tenotomy of the gastrocnemius muscle. Seven days after surgery there was an increase in the wet weight of the soleus (Sol) and plantaris (P) muscles and a decrease in that of the gastrocnemius (G) muscle from the tenotomized limb compared with the respective control muscles from the contralateral limb from the same animal. In all three muscles there was a significant increase in the fractional rate of protein synthesis (ks) in the muscles from the tenotomized limb above the rate of the respective control muscles. In contrast, the extensor digitorum longus (EDL) muscle showed no change in wet weight or ks 7 days after tenotomy of G. Fasting for 12 or 36 h had no significant effect on ks in G, P, or Sol muscles from either the control or tenotomized limbs. In EDL from the control limb, both fasting periods resulted in a significant decrease in ks, although this effect was not seen in the EDL from the tenotomized limbs of the same animals. A subsequent 30-min insulin infusion was similarly ineffectual in G, P, and Sol, with its only effect evident in the EDL from the control limb, where it was sufficient to reverse the decreased ks resulting from the fasting, even though after 36 h fasting the reversal was only partial.     

Abnormalities in structure and function of limb skeletal muscle fibres of dystrophic mdx mice.

In this study we have shown that the skeletal muscle fibres from adult (older than 26 weeks) mdx mice have gross structural deformities. We have characterized the onset and age dependence of this feature in mdx mice. The three dimensional structure of these deformities has been visualized in isolated fibres and the orientation of these deformities was determined within the muscle by confocal laser scanning microscopy. We have also shown that the occurrence of morphologically abnormal fibres is greater in muscles with longer fibres (extensor digitorum longus (EDL) and soleus, 6-7.3 mm long), than in muscles with shorter fibres (flexor digitorum brevis (FDB), 0.3-0.4 mm long). A population of post-degenerative fibres, with both central and peripheral nuclei coexistent along the length of the fibre, has also been identified in the muscles studied. We showed that a mild protocol of lengthening (eccentric) contractions (the muscle was stretched by 12% during a tetanic contraction) caused a major reduction in the maximal tetanic force subsequently produced by mdx EDL muscle. In contrast, maximal tetanic force production in normal soleus, normal EDL and mdx soleus muscles was not altered by this protocol. We suggest that the deformed fast glycolytic fibres which are found in adult mdx EDL but not in adult mdx soleus muscles are the population of fibres damaged by the lengthening protocol.     

Recovery after intense chronic stimulation: a physiological study of cat's fast muscle

Adult cats were used to study the recovery of muscles that had become altered by long-term electrical stimulation. Chronic activation was delivered to the deafferented common peroneal nerve (no pain, no reflexes), and contractile properties were measured for peroneus longus muscle. After 4 wk of great daily amounts of treatment at moderately high pulse rates (30-40 Hz delivered during 50% of daily time), the peroneus longus became considerably weaker, demonstrated a longer time course of twitches and a slower rate of rise of tetanic force, and became less fatigable. Furthermore, its twitch-to-tetanus ratio decreased, and there was no longer any depression of electromyogram (EMG) amplitude during fatigue tests. After 4 wk of subsequent rest it was found that 1) twitch speed and maximum tetanic force had returned to nearly normal values, 2) fatigue resistance showed some return toward normal but was still significantly enhanced, and 3) no significant recovery had yet occurred of the altered twitch-to-tetanus ratio, the abolished EMG depression, or the slowed rate of rise of tetanic tension. During the poststimulation recovery period, the progressive increase of isometric twitch speed was not promoted by the administration of small daily amounts of high-rate stimulation (100-Hz bursts). The results support the conclusions that 1) the time course of recovery differs among physiological properties, 2) the EMG and force reactions that occur during a fatigue test are not strongly coupled, as demonstrated by the alterations of their relationship during poststimulation recovery, and 3) in cat's fast muscles, there is still no evidence for rate-specific effects of chronic stimulation on isometric twitch speed.     

Structure and function of skeletal muscle in zebrafish early larvae

Zebrafish muscles were examined at an early developmental stage (larvae 5-7 d). Using aluminum clips, preparations (approximately 1.5 mm length, 150 microm diameter) were mounted for force registration and small angle x-ray diffraction. Sarcomeres were oriented mainly in parallel with the preparation long axis. Electrical stimulation elicited fast and reproducible single twitch contractions. Length-force relations showed an optimal sarcomere length of 2.15 microm. X-ray diffraction revealed clear equatorial 1.1/1.0 reflections, showing that myofilaments are predominantly arranged along the preparation long axis. In contrast, reflections from older (2 mo) zebrafish showed two main filament orientations each at an approximately 25 degrees angle relative to the preparation long axis. Electrical stimulation of larvae muscles increased the 1.1/1.0 intensity ratio, reflecting mass transfer to thin filaments during contraction. The apparent lattice volume was 3.42 x 10(-3) microm(3), which is smaller than that of mammalian striated muscle and more similar to that of frog muscles. The relation between force and stimulation frequency showed fusion of responses at a comparatively high frequency (approximately 186 Hz), reflecting a fast muscle phenotype. Inhibition of fast myosin with N-benzyl-p-toluene sulphonamide (BTS) showed that the later phase of the tetanus was less affected than the initial peak. This suggests that, although the main contractile phenotype is fast, slow twitch fibers can contribute to sustained contraction. A fatigue stimulation protocol with repeated 220 ms/186 Hz tetani showed that tetanic force decreased to 50% at a train rate of 0.1 s(-1). In conclusion, zebrafish larvae muscles can be examined in vitro using mechanical and x-ray methods. The muscles and myofilaments are mainly orientated in parallel with the larvae long axis and exhibit a significant fast contractile component. Sustained contractions can also involve a small contribution from slower muscle types.     

Effect of neurogenic inactivity on posttetanic responses of rat fast muscle

At a short-term tetanic stimulation of fast muscle in response to subsequent single stimulation there is recorded a temporary increase of the strength of single contractions that returns to the initial background after 6–10 min. This phenomenon is called posttetanic potentiation (PTP) and is recorded only in fast muscles. The goal of the present work was a study of effect of motor innervation on the course of PTP in rat m. extensor digitorum longus (m. Edl). It has been established that the first signs of effect of motor denervation on the PTP course after section of sciatic nerve in the area of popliteal fossa are recorded as early as at the 4th day after denervation and are expressed in a decrease of strength of single contractions after cessation of tetanic stimulation. These changes reach its maximum at the 14–15th day after denervation when effect of PTP in denervated muscle does not appear at all. Pharmacological analysis of the studied phenomenon has shown that dantrolen (10 μM) suppresses amplitude of the single contraction, but does not prevent the appearance of PTP in intact muscle. In the denervated m. Edl, instead of the appearance of PTP, after a brief slight increase, a gradual decrease of the strength of contraction is recorded. Thus, it can be concluded that no significant PTP changes are present under action of dantrolen. It has been established that after the 10-min muscle incubation in Ringer’s solution with caffeine (4 mM), strength of the single contraction in intact and denervated muscles increases by approximately equal value. Tetanization of intact muscle increases strength of the single contraction approximately by 7% more than this occurs after incubation with caffeine, i.e., this substance reduces the capability of muscle for the appearance of PTP. On denervated muscle, caffeine increases strength of singly contraction, but does not potentiate development of PTP. The obtained data allow concluding about the existence of different mechanisms underlying the pretetatnic contraction and posttetanic potentiation of the single contraction. The main difference between two types of contractions can be recruiting of additional DICR-channels in the process of contraction under conditions of PTP.     

Enhanced Ca2+ transport and muscle relaxation in skeletal muscle from sarcolipin-null mice

Sarcolipin (SLN) inhibits sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) pumps. To evaluate the physiological significance of SLN in skeletal muscle, we compared muscle contractility and SERCA activity between Sln-null and wild-type mice. SLN protein expression in wild-type mice was abundant in soleus and red gastrocnemius (RG), low in extensor digitorum longus (EDL), and absent from white gastrocnemius (WG). SERCA activity rates were increased in soleus and RG, but not in EDL or WG, from Sln-null muscles, compared with wild type. No differences were seen between wild-type and Sln-null EDL muscles in force-frequency curves or maximum rates of force development (+dF/dt). Maximum relaxation rates (-dF/dt) of EDL were higher in Sln-null than wild type across a range of submaximal stimulation frequencies, but not during a twitch or peak tetanic contraction. For soleus, no differences were seen between wild type and Sln-null in peak tetanic force or +dF/dt; however, force-frequency curves showed that peak force during a twitch and 10-Hz contraction was lower in Sln-null. Changes in the soleus force-frequency curve corresponded with faster rates of force relaxation at nearly all stimulation frequencies in Sln-null compared with wild type. Repeated tetanic stimulation of soleus caused increased (-dF/dt) in wild type, but not in Sln-null. No compensatory responses were detected in analysis of other Ca(2+) regulatory proteins using Western blotting and immunohistochemistry or myosin heavy chain expression using immunofluorescence. These results show that 1) SLN regulates Ca(2+)-ATPase activity thereby regulating contractile kinetics in at least some skeletal muscles, 2) the functional significance of SLN is graded to the endogenous SLN expression level, and 3) SLN inhibitory effects on SERCA function are relieved in response to repeated contractions thus enhancing relaxation rates.     

Effect of insulin on characteristics of contractile responses of fast and slow skeletal muscles of rats with acute streptozotocin-induced diabetes

Comparison of amplitude-time characteristics of fast extensor digitorum longus muscles (m. EDL) isolated from control rats and rats with model of acute streptozotocin-induced diabetes mellitus (DM) 12 and 30 days after treatment with streptozotozin did not reveal significant changes of strength of single normalized contractile responses as compared with control. In slow (m. Soleus) muscles of rats with the 30-day long SD, essential changes of the amplitude-time characteristics of such contractile responses were observed: a decrease of their amplitude and an increase of duration. In the diabetic rats treated with insulin there develops resistance of skeletal muscles of both types to action of exogenous insulin. Both in control and in diabetic animals the exhausting stimulation of m. EDL with trains from 5 impulses did not reveal significant differences at early (up to 3 min) terms of development of fatigue. Under similar conditions, fatigue of m. Soleus in rats of the both diabetic groups developed significantly faster as compared with control (already in 30 s after the beginning of stimulation). Insulin at a concentration of 0.5–1 nM produced a dose-dependent decrease of amplitude of single contractile responses in fast and slow muscles of rats with the acute SD model (the negative inotropic action). Earlier, we demonstrated in healthy rats the similar action of insulin, but at the higher concentrations [1]. Insulin at a concentration of 10 nM did not produce an essential effect on dynamics of depression of responses in the course of development of fatigue at tetanical stimulation of m. EDL and m. Soleus both in control and in diabetic rats, but affected essentially the dynamics of change of duration of the half-decay (T_hd) of their tetanical responses. The presence of insulin in the washing solution led to stabilization of the period of muscle relaxation in the course of development of fatigue in all studied animal groups.     

Lipoprotein lipase activity in skeletal muscles of the rat: effects of denervation and tenotomy.

The effects of denervation, tenotomy, or tenotomy with simultaneous denervation on the activity of heparin-releasable and intracellular, residual lipoprotein lipase (LPL) and triacylglycerol (TG) content were examined in rat skeletal muscles. An influence of muscle electrostimulation on denervated and tenotomized muscles was also evaluated. Activity of both LPL fractions was decreased in denervated and/or tenotomized soleus and red portion of gastrocnemius muscles. It was accompanied by a slight elevation of the intracellular TG content. Electrostimulation increased activities of both fractions of LPL in red muscles from intact hindlimbs. In stimulated denervated muscles without or with simultaneous tenotomy, activity of two LPL fractions was also enhanced, but control values were reached only in denervated soleus muscle. Electrical stimulation had no pronounced effect on LPL activity in tenotomized muscles. In conclusion, denervation and/or tenotomy decreases LPL activity in red muscles, indicating reduction of the muscle potential to utilize circulating TG. Electrostimulation only partly restores the diminished LPL activity in denervated muscles, without any effect in tenotomized ones. Thus, to maintain LPL activity in resting muscle, intact innervation and tension are needed.     

Chronic hypobaric hypoxia increases isolated rat fast-twitch and slow-twitch limb muscle force and fatigue

Chronic hypoxia alters respiratory muscle force and fatigue, effects that could be attributed to hypoxia and/or increased activation due to hyperventilation. We hypothesized that chronic hypoxia is associated with phenotypic change in non-respiratory muscles and therefore we tested the hypothesis that chronic hypobaric hypoxia increases limb muscle force and fatigue. Adult male Wistar rats were exposed to normoxia or hypobaric hypoxia (PB=450 mm Hg) for 6 weeks. At the end of the treatment period, soleus (SOL) and extensor digitorum longus (EDL) muscles were removed under pentobarbitone anaesthesia and strips were mounted for isometric force determination in Krebs solution in standard water-jacketed organ baths at 25 °C. Isometric twitch and tetanic force, contractile kinetics, force-frequency relationship and fatigue characteristics were determined in response to electrical field stimulation. Chronic hypoxia increased specific force in SOL and EDL compared to age-matched normoxic controls. Furthermore, chronic hypoxia decreased endurance in both limb muscles. We conclude that hypoxia elicits functional plasticity in limb muscles perhaps due to oxidative stress. Our results may have implications for respiratory disorders that are characterized by prolonged hypoxia such as chronic obstructive pulmonary disease (COPD).     

Tenotomy of the avian anterior latissimus dorsi muscle. I. Effect of age on fiber-type transformation and regeneration from the stump in chicks

The chick's anterior latissimus dorsi muscle (ALD) was tenotomized at its origin at either 1 day or 4 weeks of age, and investigated histochemically and ultrastructurally at intervals thereafter to determine whether muscle fiber-type transformation from a slow to a twitch type is greater in young birds than older birds. No transformation of fiber type occurred in either procedure, but a new muscular connection regenerated between the scar tissue at the end of the original tenotomized stump and the former origin. This regenerated muscle had a mosaic pattern of fiber types, as demonstrated by myofibrillar ATPase activity, and contained predominantly fast fibers, as contrasted with controls or the tenotomized portion, which contained predominantly slow tonic muscle fibers. The regenerated portion contained muscle spindles. The original portion of the tenotomized muscle was indistinguishable from the control muscle. These responses of the chick ALD to tenotomy are quite different from those in the pigeon, which are reported in the following study.     

Transformation of individual contractile responses during tetanus in rat fast and slow skeletal muscles

Using a computer graphics approach, the last contractile responses (LCR_N, where N is a number of elementary contractile responses in tetanus) were separated from integral tetanic responses of rat fast muscles, m. Eхtensor digitorum longus (m. EDL), and slow muscles, m. Soleus, evoked by trains of 5, 10 and 50 stimuli. In m. Soleus, at a stimulation frequency of 20 Hz, the LCR₅ average amplitude decreased to 64 ± 9% compared to the single contraction amplitude. As N increased, LCR_N recovered and then rose to the values exceeding almost twofold initial elementary contractile responses (up to 211 ± 10% for LCR₅₀). Simultaneously, against the background of rising elementary contractile responses, a significant shortening of their half-decay time (～by 50%) and the formation of a stationary plateau within LCR_N was observed. In m. EDL, at a stimulation frequency of 50 Hz, there was only a single-phase LCR_N rise (up to 165 ± 18% for LCR₅₀) without changes in half-decay time and plateau formation. In skeletal muscles of both types, the prolonged (up to 30 s) ‘hyper-relaxation effect’ was found to develop after the end of tetanic responses manifested as a reduction of muscle tension followed by its recovery to the initial level. Possible mechanisms of these events are discussed. It is hypothesized that transformation of elementary contractile responses in skeletal muscles can be fulfilled due to the existence of specialized microdomains in muscle fibers which regulate accumulation and extrusion of Ca²⁺ ions during tetanic activity. The possibility that the basic, depolarization-induced, Ca²⁺ release (DICR) is complemented by an additional, Ca²⁺-induced, Ca²⁺release (CIRC) is analyzed.     

The effect of two episodes of denervation and reinnervation on skeletal muscle contractile function.

Sensory or motor "baby-sitting" has been proposed as a clinical strategy to preserve muscle integrity if motion-specific axons must regenerate over a long distance to reach denervated target muscles. Denervated muscles are innervated temporarily by using axons from nearby sensory or motor nerves. After motion specific motor axons have reached the target, the baby-sitter nerve is severed and motion-specific axons are directed to the target. Although this strategy minimizes denervation time, the requisite second episode of denervation and reinnervation might be deleterious to muscle contractile function. This study was designed to test the hypothesis that two sequential episodes of skeletal muscle denervation and reinnervation result in greater force and power deficits than a single peripheral nerve injury and repair. Adult Lewis rats underwent either transection and epineurial repair or sham exposure of the left peroneal nerve. After a 4-month recovery period, the contractile properties of the extensor digitorum longus muscle of the sham exposure group (control, n = 9) and one of the nerve division and repair groups (repair group 1, n = 9) were evaluated with measurements of the maximum tetanic isometric force, peak power, and maximal sustained power. A third group of rats underwent a second cycle of nerve division and repair (repair group 2, n = 9) at this same time point. Four months postoperatively, contractile properties of the extensor digitorum longus muscles were evaluated. Maximum tetanic isometric force and peak power were significantly reduced in repair group 2 rats as compared with repair group 1 and control rats. Maximal sustained power was not significantly different between the groups. These data support our working hypothesis that skeletal muscle contractile function is adversely affected by two cycles of denervation and reinnervation as compared with a single episode of nerve division and repair.     

Denervated muscle fibers explain the deficit in specific force following reinnervation of the rat extensor digitorum longus muscle

The authors tested the hypothesis that, after denervation and reinnervation of skeletal muscle, observed deficits in specific force can be completely attributed to the presence of denervated muscle fibers. The peroneal nerve innervating the extensor digitorum longus muscle in rats was sectioned and the distal stump was coapted to the proximal stump, allowing either a large number of motor axons (nonreduced, n = 12) or a drastically reduced number of axons access to the distal nerve stump (drastically reduced, n = 18). A control group of rats underwent exposure of the peroneal nerve, without transection, followed by wound closure (control, n = 9). Four months after the operation, the maximum tetanic isometric force (Fo) of the extensor digitorum longus muscle was measured in situ and the specific force (sFo) was calculated. Cross-sections of the muscles were labeled for neural cell adhesion molecule (NCAM) protein to distinguish between innervated and denervated muscle fibers. Compared with extensor digitorum longus muscles from rats in the control (295 +/- 11 kN/m2) and nonreduced (276 +/- 12 kN/m2) groups, sFo of the extensor digitorum longus muscles from animals in the drastically reduced group was decreased (227 +/- 15 kN/m2, p < 0.05). The percentage of denervated muscle fibers in the extensor digitorum longus muscles from animals in the drastically reduced group (18 +/- 3 percent) was significantly higher than in the control (3 +/- 1 percent) group, but not compared with the nonreduced (9 +/- 2 percent) group. After exclusion of the denervated fibers, sFo did not differ between extensor digitorum longus muscles from animals in the drastically reduced (270 +/- 20 kN/m2), nonreduced (301 +/- 13 kN/m2), or control (303 +/- 10 kN/m2) groups. The authors conclude that, under circumstances of denervation and rapid reinnervation, the decrease in sFo of muscle can be attributed to the presence of denervated muscle fibers.     

Electrolysis stimulates creatine transport and transporter cell surface expression in incubated mouse skeletal muscle: potential role of ROS

Electrical field stimulation of isolated, incubated rodent skeletal muscles is a frequently used model to study the effects of contractions on muscle metabolism. In this study, this model was used to investigate the effects of electrically stimulated contractions on creatine transport. Soleus and extensor digitorum longus muscles of male NMRI mice (35-50 g) were incubated in an oxygenated Krebs buffer between platinum electrodes. Muscles were exposed to [(14)C]creatine for 30 min after either 12 min of repeated tetanic isometric contractions (contractions) or electrical stimulation of only the buffer before incubation of the muscle (electrolysis). Electrolysis was also investigated in the presence of the reactive oxygen species (ROS) scavenging enzymes superoxide dismutase (SOD) and catalase. Both contractions and (to a lesser degree) electrolysis stimulated creatine transport severalfold over basal. The amount of electrolysis, but not contractile activity, induced (determined) creatine transport stimulation. Incubation with SOD and catalase at 100 and 200 U/ml decreased electrolysis-induced creatine transport by approximately 50 and approximately 100%, respectively. The electrolysis effects on creatine uptake were completely inhibited by beta-guanidino propionic acid, a competitive inhibitor of (creatine for) the creatine transporter (CRT), and were accompanied by increased cell surface expression of CRT. Muscle glucose transport was not affected by electrolysis. The present results indicate that electrical field stimulation of incubated mouse muscles, independently of contractions per se, stimulates creatine transport by a mechanism that depends on electrolysis-induced formation of ROS in the incubation buffer. The increased creatine uptake is paralleled by an increased cell surface expression of the creatine transporter.     

Nitric oxide synthase expression and effects of nitric oxide modulation on contractility of rat extraocular muscle.

Extraocular muscles (EOMs) are specialized skeletal muscles that are constantly active, generate low levels of force for cross sectional area, have rapid contractile speeds, and are highly fatigue resistant. The neuronal isoform of nitric oxide synthase (nNOS) is concentrated at the sarcolemma of fast-twitch muscles fibers, and nitric oxide (NO) modulates contractility. This study evaluated nNOS expression in EOM and the effect of NO modulation on lateral rectus muscle's contractility. nNOS activity was highest in EOM compared with diaphragm, extensor digitorum longus, and soleus. Neuronal NOS was concentrated to the sarcolemma of orbital and global singly innervated fibers, but not evident in the multi-innervated fibers. The NG-nitro-L-arginine methyl ester (L-NAME, a NOS inhibitor), increased submaximal tetanic and peak twitch forces. The NO donors S-nitroso-N-acetylcysteine (SNAC) and spermineNONOate reduced submaximal tetanic and peak twitch forces. The effect of NO on the contractile force of lateral rectus muscle is greater than previously observed on other skeletal muscle. NO appears more important in modulating contraction of EOM compared with other skeletal muscles, which could be important for the EOM's specialized role in generation of eye movements.     

Effects of aging on the lateral transmission of force in rat skeletal muscle

The age-related reduction in muscle force cannot be fully explained by the loss of muscle fiber mass or degeneration of myofibers. Our previous study showed that changes in lateral transmission of force could affect the total force transmitted to the tendon. The extracellular matrix (ECM) of skeletal muscle plays an important role in lateral transmission of force. The objective of this study was to define the effects of aging on lateral transmission of force in skeletal muscles, and explore possible underlying mechanisms. In vitro contractile tests were performed on extensor digitorum longus (EDL) muscle of young and old rats with series of tenotomy and myotomy. We concluded that lateral transmission of force was impaired in the old rats, and this deficit could be partly due to increased thickness of the ECM induced by aging.     

Altered Contractility of Skeletal Muscle in Mice Deficient in Titin’s M-Band Region

We investigated the contractile phenotype of skeletal muscle deficient in exons MEx1 and MEx2 (KO) of the titin M-band by using the cre-lox recombination system and a multidisciplinary physiological approach to study skeletal muscle contractile performance. At a maximal tetanic stimulation frequency, intact KO extensor digitorum longus muscle was able to produce wild-type levels of force. However, at submaximal stimulation frequency, force was reduced in KO mice, giving rise to a rightward shift of the force-frequency curve. This rightward shift of the force-frequency curve could not be explained by altered sarcoplasmic reticulum Ca²⁺ handling, as indicated by analysis of Ca²⁺ transients in intact myofibers and expression of Ca²⁺-handling proteins, but can be explained by the reduced myofilament Ca²⁺ sensitivity of force generation that we found. Western blotting experiments suggested that the excision of titin exons MEx1 and MEx2 did not result in major changes in expression of titin M-band binding proteins or phosphorylation level of the thin-filament regulatory proteins, but rather in a shift toward expression of slow isoforms of the thick-filament-associated protein, myosin binding protein-C. Extraction of myosin binding protein-C from skinned muscle normalized myofilament Ca²⁺ sensitivity of the KO extensor digitorum longus muscle. Thus, our data suggest that the M-band region of titin affects the expression of genes involved in the regulation of skeletal muscle contraction.     

Differential Effect of Denervation on Free-Radical Scavenging Enzymes in Slow and Fast Muscle of Rat

To determine the effect of denervation on the free-radical scavenging systems in relation to the mitochondrial oxidative metabolism in the slow-twitch soleus and fast-twitch extensor digitorum longus (EDL) muscles, the sciatic nerve of the rat was crushed in the midthigh region and the muscle tissue levels of five enzymes were studied 2 and 5 weeks following crush. Recently developed radioimmunoassays were utilized for the selective measurement of cuprozinc (cytosolic) and mangano (mitochondrial) superoxide dismutases. Total tissue content of cuprozinc superoxide dismutase showed a mild decrease after denervation in slow but not in fast muscle. Manganosuperoxide dismutase and fumarase decreased markedly at 2 weeks and returned toward control levels by 5 weeks, the changes appearing to be greater in slow than in fast muscle. At 2 weeks, cytochrome c oxidase decreased significantly in slow, but not in fast muscle. GSH-peroxidase at baseline was 10-fold higher in slow than in fast muscle, markedly decreased at 2 weeks in slow muscle, and returned toward control levels at 5 weeks, whereas the total enzyme activity in fast muscle did not change through 5 weeks. These data represent the first systematic report of free radical scavenging systems in slow and fast muscles in response to denervation. Selective modification of cuprozinc and manganosuperoxide dismutases and differential regulation of GSH-peroxidase was demonstrated in slow and fast muscle.     

Skeletal muscle relaxation rate after fasting or hypocaloric feeding

The effect of malnutrition on skeletal muscle relaxation is not entirely clear; some studies indicate no change and others a slowing of the relaxation rate. We investigated whether these different results were due to type of malnutrition, muscle fiber type composition, or the index used to express relaxation rate. The effect of a 2-day fast (16% body wt loss) or 1 wk of hypocaloric feeding (22.6% wt loss) on relaxation rates of soleus and extensor digitorum longus (EDL) muscles was studied in situ with the use of anesthetized adult Wistar rats. Relaxation rates were assessed for twitch contractions using half-relaxation times and exponential phase half-times and for tetanic contractions using exponential phase half-times. The rate of relaxation was unaffected by fasting, whereas hypocaloric feeding reduced relaxation rates after twitch and tetanic contractions in both soleus and EDL muscles. We conclude that slowing of skeletal muscle relaxation rate occurs after 1 wk of hypocaloric feeding but not after 2 days of fasting. The slowing is independent of muscle fiber composition, type of contraction, or the index used to express relaxation rate.