Effects of prolonged space flight on human skeletal muscle enzyme and substrate profiles.

Our primary goal was to determine the effects of 6-mo flight on the International Space Station (ISS) on selected anaerobic and aerobic enzymes, and the content of glycogen and lipids in slow and fast fibers of the soleus and gastrocnemius. Following local anesthesia, biopsies were obtained from nine ISS crew members ∼45 days preflight and on landing day (R+0) postflight. We subdivided the crew into those who ran 200 min/wk or more (high treadmill, HT) in-flight from those who ran <100 min/wk (low treadmill, LT). In the LT group, there was a loss of lipid in soleus type I fibers, and muscle glycogen significantly increased in soleus fiber types postflight. Soleus cytochrome oxidase (CO) activity was significantly depressed postflight in the type I fiber. This was attributed to the LT group where CO activity was reduced 59%. Otherwise, there was no change in the crew mean for type I or IIa fiber glycolytic or mitochondrial enzyme activities pre- vs. postflight in either muscle. However, two of the three HT subjects (Subjects E and H) showed significant increases in both ß-hydroxyacyl-CoA dehydrogenase and citrate synthase in the soleus type I fibers, and Subject E, exhibiting the largest increase in soleus oxidative enzymes, was the only subject to show a significant decrease in glycolytic enzyme activity. It is apparent that crew members performing adequate treadmill running can maintain calf muscle enzymes, which suggests that increased fatigue with weightlessness cannot be directly caused by a decline in muscle enzyme capacity.

Prolonged space flight-induced alterations in the structure and function of human skeletal muscle fibres.

The primary goal of this study was to determine the effects of prolonged space flight (180 days) on the structure and function of slow and fast fibres in human skeletal muscle. Biopsies were obtained from the gastrocnemius and soleus muscles of nine International Space Station crew members 45 days pre- and on landing day (R+0) post-flight. The main findings were that prolonged weightlessness produced substantial loss of fibre mass, force and power with the hierarchy of the effects being soleus type I > soleus type II > gastrocnemius type I > gastrocnemius type II. Structurally, the quantitatively most important adaptation was fibre atrophy, which averaged 20% in the soleus type I fibres (98 to 79 µm diameter). Atrophy was the main contributor to the loss of peak force (P(0)), which for the soleus type I fibre declined 35% from 0.86 to 0.56 mN. The percentage decrease in fibre diameter was correlated with the initial pre-flight fibre size (r = 0.87), inversely with the amount of treadmill running (r = 0.68), and was associated with an increase in thin filament density (r = 0.92). The latter correlated with reduced maximal velocity (V(0)) (r = 0.51), and is likely to have contributed to the 21 and 18% decline in V(0) in the soleus and gastrocnemius type I fibres. Peak power was depressed in all fibre types with the greatest loss (55%) in the soleus. An obvious conclusion is that the exercise countermeasures employed were incapable of providing the high intensity needed to adequately protect fibre and muscle mass, and that the crew's ability to perform strenuous exercise might be seriously compromised. Our results highlight the need to study new exercise programmes on the ISS that employ high resistance and contractions over a wide range of motion to mimic the range occurring in Earth's 1 g environment.

The deleterious effects of bed rest on human skeletal muscle fibers are exacerbated by hypercortisolemia and ameliorated by dietary supplementation.

Prolonged inactivity associated with bed rest in a clinical setting or spaceflight is frequently associated with hypercortisolemia and inadequate caloric intake. Here, we determined the effect of 28 days of bed rest (BR); bed rest plus hypercortisolemia (BRHC); and bed rest plus essential amino acid (AA) and carbohydrate (CHO) supplement (BRAA) on the size and function of single slow- and fast-twitch muscle fibers. Supplementing meals, the BRAA group consumed 16.5 g essential amino acids and 30 g sucrose at 1100, 1600, and 2100 h, and the BRHC subjects received 5 daily doses of 10-15 mg of oral hydrocortisone sodium succinate throughout bed rest. Bed rest induced atrophy and loss of force (mN) and power (muN.FL.s(-1)) in single fibers was exacerbated by hypercortisolemia where soleus peak force declined by 23% in the type I fiber from a prevalue of 0.78 +/- 0.02 to 0.60 +/- 0.02 mN post bed rest (compared to a 7% decline with bed rest alone) and 27% in the type II fiber (1.10 +/- 0.08 vs. 0.81 +/- 0.05 mN). In the BRHC group, peak power dropped by 19, 15, and 11% in the soleus type I, and vastus lateralis (VL) type I and II fibers, respectively. The AA/CHO supplement protected against the bed rest-induced loss of peak force in the type I soleus and peak power in the VL type II fibers. These results provide evidence that an AA/CHO supplement might serve as a successful countermeasure to help preserve muscle function during periods of relative inactivity.

Low cell pH depresses peak power in rat skeletal muscle fibres at both 30 degrees C and 15 degrees C: implications for muscle fatigue.

Historically, an increase in intracellular H(+) (decrease in cell pH) was thought to contribute to muscle fatigue by direct inhibition of the cross-bridge leading to a reduction in velocity and force. More recently, due to the observation that the effects were less at temperatures closer to those observed in vivo, the importance of H(+) as a fatigue agent has been questioned. The purpose of this work was to re-evaluate the role of H(+) in muscle fatigue by studying the effect of low pH (6.2) on force, velocity and peak power in rat fast- and slow-twitch muscle fibres at 15 degrees C and 30 degrees C. Skinned fast type IIa and slow type I fibres were prepared from the gastrocnemius and soleus, respectively, mounted between a force transducer and position motor, and studied at 15 degrees C and 30 degrees C and pH 7.0 and 6.2, and fibre force (P(0)), unloaded shortening velocity (V(0)), force-velocity, and force-power relationships determined. Consistent with previous observations, low pH depressed the P(0) of both fast and slow fibres, less at 30 degrees C (4-12%) than at 15 degrees C (30%). However, the low pH-induced depressions in slow type I fibre V(0) and peak power were both significantly greater at 30 degrees C (25% versus 9% for V(0) and 34% versus 17% for peak power). For the fast type IIa fibre type, the inhibitory effect of low pH on V(0) was unaltered by temperature, while for peak power the inhibition was reduced at 30 degrees C (37% versus 18%). The curvature of the force-velocity relationship was temperature sensitive, and showed a higher a/P(0) ratio (less curvature) at 30 degrees C. Importantly, at 30 degrees C low pH significantly depressed the ratio of the slow type I fibre, leading to less force and velocity at peak power. These data demonstrate that the direct effect of low pH on peak power in both slow- and fast-twitch fibres at near-in vivo temperatures (30 degrees C) is greater than would be predicted based on changes in P(0), and that the fatigue-inducing effects of low pH on cross-bridge function are still substantial and important at temperatures approaching those observed in vivo.

The depressive effect of Pi on the force-pCa relationship in skinned single muscle fibers is temperature dependent.

Increases in P(i) combined with decreases in myoplasmic Ca(2+) are believed to cause a significant portion of the decrease in muscular force during fatigue. To investigate this further, we determined the effect of 30 mM P(i) on the force-Ca(2+) relationship of chemically skinned single muscle fibers at near-physiological temperature (30 degrees C). Fibers isolated from rat soleus (slow) and gastrocnemius (fast) muscle were subjected to a series of solutions with an increasing free Ca(2+) concentration in the presence and absence of 30 mM P(i) at both low (15 degrees C) and high (30 degrees C) temperature. In slow fibers, 30 mM P(i) significantly increased the Ca(2+) required to elicit measurable force, referred to as the activation threshold at both low and high temperatures; however, the effect was twofold greater at the higher temperature. In fast fibers, the activation threshold was unaffected by elevating P(i) at 15 degrees C but was significantly increased at 30 degrees C. At both low and high temperatures, 30 mM P(i) increased the Ca(2+) required to elicit half-maximal force (pCa(50)) in both slow and fast fibers, with the effect of P(i) twofold greater at the higher temperature. These data suggest that during fatigue, reductions in the myoplasmic Ca(2+) and increases in P(i) act synergistically to reduce muscular force. Consequently, the combined changes in these ions likely account for a greater portion of fatigue than previously predicted based on studies at lower temperatures or high temperatures at saturating Ca(2+) levels.

Skeletal muscle fiber atrophy: altered thin filament density changes slow fiber force and shortening velocity.

Single skinned fibers from soleus and adductor longus (AL) muscles of weight-bearing control rats and rats after 14-day hindlimb suspension unloading (HSU) were studied physiologically and ultrastructurally to investigate how slow fibers increase shortening velocity (V0) without fast myosin. We hypothesized that unloading and shortening of soleus during HSU reduces densities of thin filaments, generating wider myofilament separations that increase V0 and decrease specific tension (kN/m2). During HSU, plantarflexion shortened soleus working length 23%. AL length was unchanged. Both muscles atrophied as shown by reductions in fiber cross-sectional area. For AL, the 60% atrophy accounted fully for the 58% decrease in absolute tension (mN). In the soleus, the 67% decline in absolute tension resulted from 58% atrophy plus a 17% reduction in specific tension. Soleus fibers exhibited a 25% reduction in thin filaments, whereas there was no change in AL thin filament density. Loss of thin filaments is consistent with reduced cross bridge formation, explaining the fall in specific tension. V0 increased 27% in soleus but was unchanged in AL. The V0 of control and HSU fibers was inversely correlated (R = -0.83) with thin filament density and directly correlated (R = 0.78) with thick-to-thin filament spacing distance in a nonlinear fashion. These data indicate that reduction in thin filament density contributes to an increased V0 in slow fibers. Osmotically compacting myofilaments with 5% dextran returned density, spacing, and specific tension and slowed V0 to near-control levels and provided evidence for myofilament spacing modulating tension and V0.

Contractile responses of the rat gastrocnemius and soleus muscles to isotonic resistance exercise.

Male rats were divided into control and weight-trained (WT) groups. WT rats performed squat-type exercises twice daily, 5 days/wk, for 14 wk. They averaged 36 lifts/day, with an average weight of 555 g. Muscle-to-body weight ratio (mg/g) of the soleus (Sol) was not different from control, but it increased 11 and 6% in the gastrocnemius (Gast) and plantaris, respectively (P < 0.05). The normalized twitch tension of the in situ Sol was elevated by 21%, whereas single-skinned type I fibers from the Sol showed an increased rate constant of tension redevelopment (K(tr)) but no other contractile adaptations to WT. In contrast, the Gast type I fibers showed an increase (P < 0.05) in maximal velocity of shortening (25%), peak power (15%), K(tr) (18%), and normalized tension (7%). The K(tr) and normalized tension of the Gast type IIa fibers increased by 24% (P < 0.05) and 12% (P < 0.05), respectively, whereas velocity and power showed a tendency to increase. Fiber size, determined by myosin ATPase histochemistry, was not different for any fiber type from the Gast or Sol. These results indicate that isotonic resistance exercise of the calf targets the Gast (type I and type IIa fibers) and has little effect on the Sol.

Passive stretch inhibits central corelike lesion formation in the soleus muscles of hindlimb-suspended unloaded rats.

Hindlimb suspension unloading (HSU) is a ground-based model simulating the effects of microgravity unloading on the musculoskeletal system. In this model, gravity causes the hind foot of the rat to drop, opening the front of the ankle to 90-105 degrees plantar flexion at rest. As HSU proceeds, the normal weight-bearing angle of 30 degrees dorsiflexion is achieved progressively less, and the contraction range of soleus is abbreviated. Our laboratory reported that 12 days of HSU caused central corelike lesions (CCLs) of myofibril breakdown (Riley DA, Slocum GR, Bain JL, Sedlak FR, Sowa TE, and Mellender JW. J Appl Physiol. 69: 58-66, 1990). The present study investigated whether daily stretch of the calf muscles prevents CCL formation. The soleus muscles of HSU Sprague-Dawley male rats (approximately 287 g) were lengthened by unilateral ankle splinting at 30 degrees. Compared with the nonsplinted side, splinting for 10 or 20 min per day in awake rats significantly decreased CCLs in soleus by 88 and 91%, respectively (P < 0.01). Compared with control muscle wet weight, 20-min splinting reduced atrophy by 33%, whereas 10-min splinting ameliorated atrophy by 17% (P < 0.01). Bilateral soleus electromyograph recording revealed higher levels of contractile activity on the splinted side during splinting. To isolate the effects of stretch from isometric contractile activity, contractions were eliminated by whole animal anesthesia with isoflurane during 10-min daily splinting. The percentage of fibers with CCLs was reduced by 57%, and the average lesion size was 29% smaller in the stretched muscle (P < 0.05). Soleus muscle wet weight and fiber area were unaltered by stretch alone. Loaded contractions during splinting are necessary to prevent muscle fiber atrophy. Passive muscle stretch acts to maintain myofibril structural integrity.

Fiber type and temperature dependence of inorganic phosphate: implications for fatigue.

Elevated levels of P(i) are thought to cause a substantial proportion of the loss in muscular force and power output during fatigue from intense contractile activity. However, support for this hypothesis is based, in part, on data from skinned single fibers obtained at low temperatures (< or =15 degrees C). The effect of high (30 mM) P(i) concentration on the contractile function of chemically skinned single fibers was examined at both low (15 degrees C) and high (30 degrees C) temperatures using fibers isolated from rat soleus (type I fibers) and gastrocnemius (type II fibers) muscles. Elevating P(i) from 0 to 30 mM at saturating free Ca(2+) levels depressed maximum isometric force (P(o)) by 54% at 15 degrees C and by 19% at 30 degrees C (P < 0.05; significant interaction) in type I fibers. Similarly, the P(o) of type II fibers was significantly more sensitive to high levels of P(i) at the lower (50% decrease) vs. higher temperature (5% decrease). The maximal shortening velocity of both type I and type II fibers was not significantly affected by elevated P(i) at either temperature. However, peak fiber power was depressed by 49% at 15 degrees C but by only 16% at 30 degrees C in type I fibers. Similarly, in type II fibers, peak power was depressed by 40 and 18% at 15 and 30 degrees C, respectively. These data suggest that near physiological temperatures and at saturating levels of intracellular Ca(2+), elevated levels of P(i) contribute less to fatigue than might be inferred from data obtained at lower temperatures.

Hindlimb unloading-induced muscle atrophy and loss of function: protective effect of isometric exercise.

The primary objective of this study was to determine the effectiveness of isometric exercise (IE) as a countermeasure to hindlimb unloading (HU)-induced atrophy of the slow (soleus) and fast (plantaris and gastrocnemius) muscles. Rats were assigned to either weight-bearing control, 7-day HU (H7), H7 plus IE (I7), 14-day HU (H14), or H14 plus IE (I14) groups. IE consisted of ten 5-s maximal isometric contractions separated by 90 s, administered three times daily. Contractile properties of the soleus and plantaris muscles were measured in situ. The IE attenuated the HU-induced decline in the mass and fiber diameter of the slow-twitch soleus muscle, whereas the gastrocnemius and plantaris mass were not protected. These results are consistent with the mean electromyograph recordings during IE that indicated preferential recruitment of the soleus over the gastrocnemius and plantaris muscles. Functionally, the IE significantly protected the soleus from the HU-induced decline in peak isometric force (I14, 1.49 +/- 0.12 vs. H14, 1.15 +/- 0.07 N) and peak power (I14, 163 +/- 17 vs. H14, 75 +/- 11 mN.fiber length.s-1). The exercise protocol showed protection of the plantaris peak isometric force at H7 but not H14. The IE also prevented the HU-induced decline in the soleus isometric contraction time, which allowed the muscle to produce greater tension at physiological motoneuron firing frequencies. In summary, IE resulted in greater protection from HU-induced atrophy in the slow soleus than in the fast gastrocnemius or plantaris.

Unilateral lower limb suspension does not mimic bed rest or spaceflight effects on human muscle fiber function.

We used Ca2+-activated skinned muscle fibers to test the hypothesis that unilateral lower leg suspension (ULLS) alters cross-bridge mechanisms of muscle contraction. Soleus and gastrocnemius biopsies were obtained from eight subjects before ULLS, immediately after 12 days of ULLS (post-0 h), and after 6 h of reambulation (post-6 h). Post-0 h soleus fibers expressing type I myosin heavy chain (MHC) showed significant reductions in diameter, absolute and specific peak Ca2+-activated force, unloaded shortening velocity, and absolute and normalized peak power. Fibers obtained from the gastrocnemius were less affected by ULLS, particularly fibers expressing fast MHC isoforms. Post-6 h soleus fibers produced less absolute and specific peak force than did post-0 h fibers, suggesting that reambulation after ULLS induced cell damage. Like bed rest and spaceflight, ULLS primarily affects soleus over gastrocnemius fibers. However, in contrast to these other models, slow soleus fibers obtained after ULLS showed a decrease in unloaded shortening velocity and a greater reduction in specific force.

Functional and structural adaptations of skeletal muscle to microgravity.

Our purpose is to summarize the major effects of space travel on skeletal muscle with particular emphasis on factors that alter function. The primary deleterious changes are muscle atrophy and the associated decline in peak force and power. Studies on both rats and humans demonstrate a rapid loss of cell mass with microgravity. In rats, a reduction in muscle mass of up to 37% was observed within 1 week. For both species, the antigravity soleus muscle showed greater atrophy than the fast-twitch gastrocnemius. However, in the rat, the slow type I fibers atrophied more than the fast type II fibers, while in humans, the fast type II fibers were at least as susceptible to space-induced atrophy as the slow fiber type. Space flight also resulted in a significant decline in peak force. For example, the maximal voluntary contraction of the human plantar flexor muscles declined by 20-48% following 6 months in space, while a 21% decline in the peak force of the soleus type I fibers was observed after a 17-day shuttle flight. The reduced force can be attributed both to muscle atrophy and to a selective loss of contractile protein. The former was the primary cause because, when force was expressed per cross-sectional area (kNm(-2)), the human fast type II and slow type I fibers of the soleus showed no change and a 4% decrease in force, respectively. Microgravity has been shown to increase the shortening velocity of the plantar flexors. This increase can be attributed both to an elevated maximal shortening velocity (V(0)) of the individual slow and fast fibers and to an increased expression of fibers containing fast myosin. Although the cause of the former is unknown, it might result from the selective loss of the thin filament actin and an associated decline in the internal drag during cross-bridge cycling. Despite the increase in fiber V(0), peak power of the slow type I fiber was reduced following space flight. The decreased power was a direct result of the reduced force caused by the fiber atrophy. In addition to fiber atrophy and the loss of force and power, weightlessness reduces the ability of the slow soleus to oxidize fats and increases the utilization of muscle glycogen, at least in rats. This substrate change leads to an increased rate of fatigue. Finally, with return to the 1g environment of earth, rat studies have shown an increased occurrence of eccentric contraction-induced fiber damage. The damage occurs with re-loading and not in-flight, but the etiology has not been established.

Comparison of a space shuttle flight (STS-78) and bed rest on human muscle function.

The purpose of this investigation was to assess muscle fiber size, composition, and in vivo contractile characteristics of the calf muscle of four male crew members during a 17-day spaceflight (SF; Life and Microgravity Sciences Spacelab Shuttle Transport System-78 mission) and eight men during a 17-day bed rest (BR). The protocols and timelines of these two investigations were identical, therefore allowing for direct comparisons between SF and the BR. The subjects' age, height, and weight were 43 +/- 2 yr, 183 +/- 4 cm, and 86 +/- 3 kg for SF and 43 +/- 2 yr, 182 +/- 3 cm, and 82 +/- 4 kg for BR, respectively. Calf muscle strength was examined before SF and BR; on days 2, 8, and 12 during SF and BR; and on days 2 and 8 of recovery. Muscle biopsies were obtained before and within 3 h after SF (gastrocnemius and soleus) and BR (soleus) before reloading. Maximal isometric calf strength and the force-velocity characteristics were unchanged with SF or BR. Additionally, neither SF nor BR had any effect on fiber composition or fiber size of the calf muscles studied. In summary, no changes in calf muscle strength and morphology were observed after the 17-day SF and BR. Because muscle strength is lost during unloading, both during spaceflight and on the ground, these data suggest that the testing sequence employed during the SF and BR may have served as a resistance training countermeasure to attenuate whole muscle strength loss.

Functional properties of slow and fast gastrocnemius muscle fibers after a 17-day spaceflight.

The purpose of this investigation was to study the effects of a 17-day spaceflight on the contractile properties of individual fast- and slow-twitch fibers isolated from biopsies of the fast-twitch gastrocnemius muscle of four male astronauts. Single chemically skinned fibers were studied during maximal Ca2+-activated contractions with fiber myosin heavy chain (MHC) isoform expression subsequently determined by SDS gel electrophoresis. Spaceflight had no significant effect on the mean diameter or specific force of single fibers expressing type I, IIa, or IIa/IIx MHC, although a small reduction in average absolute force (P(o)) was observed for the type I fibers (0.68 +/- 0.02 vs. 0.64 +/- 0.02 mN, P < 0.05). Subject-by-flight interactions indicated significant intersubject variation in response to the flight, as postflight fiber diameter and P(o) where significantly reduced for the type I and IIa fibers obtained from one astronaut and for the type IIa fibers from another astronaut. Average unloaded shortening velocity [V(o), in fiber lengths (FL)/s] was greater after the flight for both type I (0.60 +/- 0.03 vs. 0.76 +/- 0.02 FL/s) and IIa fibers (2.33 +/- 0.25 vs. 3.10 +/- 0.16 FL/s). Postflight peak power of the type I and IIa fibers was significantly reduced only for the astronaut experiencing the greatest fiber atrophy and loss of P(o). These results demonstrate that 1) slow and fast gastrocnemius fibers show little atrophy and loss of P(o) but increased V(o) after a typical 17-day spaceflight, 2) there is, however, considerable intersubject variation in these responses, possibly due to intersubject differences in in-flight physical activity, and 3) in these four astronauts, fiber atrophy and reductions in P(o) were less for slow and fast fibers obtained from the phasic fast-twitch gastrocnemius muscle compared with slow and fast fibers obtained from the slow antigravity soleus [J. J. Widrick, S. K. Knuth, K. M. Norenberg, J. G. Romatowski, J. L. W. Bain, D. A. Riley, M. Karhanek, S. W. Trappe, T. A. Trappe, D. L. Costill, and R. H. Fitts. J Physiol (Lond) 516: 915-930, 1999].

Fiber-type susceptibility to eccentric contraction-induced damage of hindlimb-unloaded rat AL muscles.

Slow oxidative (SO) fibers of the adductor longus (AL) were predominantly damaged during voluntary reloading of hindlimb unloaded (HU) rats and appeared explainable by preferential SO fiber recruitment. The present study assessed damage after eliminating the variable of voluntary recruitment by tetanically activating all fibers in situ through the motor nerve while applying eccentric (lengthening) or isometric contractions. Muscles were aldehyde fixed and resin embedded, and semithin sections were cut. Sarcomere lesions were quantified in toluidine blue-stained sections. Fibers were typed in serial sections immunostained with antifast myosin and antitotal myosin (which highlights slow fibers). Both isometric and eccentric paradigms caused fatigue. Lesions occurred only in eccentrically contracted control and HU muscles. Fatigue did not cause lesions. HU increased damage because lesioned- fiber percentages within fiber types and lesion sizes were greater than control. Fast oxidative glycolytic (FOG) fibers were predominantly damaged. In no case did damaged SO fibers predominate. Thus, when FOG, SO, and hybrid fibers are actively lengthened in chronically unloaded muscle, FOG fibers are intrinsically more susceptible to damage than SO fibers. Damaged hybrid-fiber proportions ranged between these extremes.

Effects of depolarization and low intracellular pH on charge movement currents of frog skeletal muscle fibers.

The low intracellular pH and membrane depolarization associated with repeated skeletal muscle stimulation could impair the function of the transverse tubular (t tubule) voltage sensor and result in a decreased sarcoplasmic reticulum Ca(2+) release and muscle fatigue. We therefore examined the effects of membrane depolarization and low intracellular pH on the t-tubular charge movement. Fibers were voltage clamped in a double Vaseline gap, at holding potential (HP) of -90 or -60 mV, and studied at an internal pH of 7.0 and 6.2. Decreasing intracellular pH did not significantly alter the maximum amount of charge moved, transition voltage, or steepness factor at either HP. Depolarizing HP significantly decreased steepness factor and maximum charge moved and shifted the transition voltage to more positive potentials. Elevated extracellular Ca(2+) decreased the depolarization-induced reduction in the charge movement. These results indicate that, although the decrease in intracellular pH seen in fatigued muscle does not impair the t-tubular charge movement, the membrane depolarization associated with muscle fatigue may be sufficient to inactivate a significant fraction of the t-tubular charge. However, if t-tubular Ca(2+) increases, some of the charge may be stabilized in the active state and remain available to initiate sarcoplasmic reticulum Ca(2+) release.

Spaceflight effects on single skeletal muscle fiber function in the rhesus monkey.

The purpose of this investigation was to understand how 14 days of weightlessness alters the cellular properties of individual slow- and fast-twitch muscle fibers in the rhesus monkey. The diameter of the soleus (Sol) type I, medial gastrocnemius (MG) type I, and MG type II fibers from the vivarium controls averaged 60 +/- 1, 46 +/- 2, and 59 +/- 2 microm, respectively. Both a control 1-G capsule sit (CS) and spaceflight (SF) significantly reduced the Sol type I fiber diameter (20 and 13%, respectively) and peak force, with the latter declining from 0.48 +/- 0.01 to 0.31 +/- 0.02 (CS group) and 0.32 +/- 0.01 mN (SF group). When the peak force was expressed as kiloNewtons per square meter (kN/m(2)), only the SF group showed a significant decline. This group also showed a significant 15% drop in peak fiber stiffness that suggests that fewer cross bridges were contracting in parallel. In the MG, SF but not CS depressed the type I fiber diameter and force. Additionally, SF significantly depressed absolute (mN) and relative (kN/m(2)) force in the fast-twitch MG fibers by 30% and 28%, respectively. The Ca(2+) sensitivity of the type I fiber (Sol and MG) was significantly reduced by growth but unaltered by SF. Flight had no significant effect on the mean maximal fiber shortening velocity in any fiber type or muscle. The post-SF Sol type I fibers showed a reduced peak power and, at peak power, an elevated velocity and decreased force. In conclusion, CS and SF caused atrophy and a reduced force and power in the Sol type I fiber. However, only SF elicited atrophy and reduced force (mN) in the MG type I fiber and a decline in relative force (kN/m(2)) in the Sol type I and MG type II fibers.

Physiology of a microgravity environment invited review: microgravity and skeletal muscle.

Spaceflight (SF) has been shown to cause skeletal muscle atrophy; a loss in force and power; and, in the first few weeks, a preferential atrophy of extensors over flexors. The atrophy primarily results from a reduced protein synthesis that is likely triggered by the removal of the antigravity load. Contractile proteins are lost out of proportion to other cellular proteins, and the actin thin filament is lost disproportionately to the myosin thick filament. The decline in contractile protein explains the decrease in force per cross-sectional area, whereas the thin-filament loss may explain the observed postflight increase in the maximal velocity of shortening in the type I and IIa fiber types. Importantly, the microgravity-induced decline in peak power is partially offset by the increased fiber velocity. Muscle velocity is further increased by the microgravity-induced expression of fast-type myosin isozymes in slow fibers (hybrid I/II fibers) and by the increased expression of fast type II fiber types. SF increases the susceptibility of skeletal muscle to damage, with the actual damage elicited during postflight reloading. Evidence in rats indicates that SF increases fatigability and reduces the capacity for fat oxidation in skeletal muscles. Future studies will be required to establish the cellular and molecular mechanisms of the SF-induced muscle atrophy and functional loss and to develop effective exercise countermeasures.

Substrate profile in rat soleus muscle fibers after hindlimb unloading and fatigue.

Limb muscles from rats flown in space and after hindlimb unloading (HU) show an increased fatigability, and spaceflight has been shown to result in a reduced ability to oxidize fatty acids. The purpose of this investigation was to determine the effects of HU on the substrate content in fast- and slow-twitch fibers and to assess the substrate utilization patterns in single slow type I fibers isolated from control and HU animals. A second objective was to assess whether HU altered the ability of the heart or limb muscle to oxidize pyruvate or palmitate. After 2 wk of HU, single fibers were isolated from the freeze-dried soleus and gastrocnemius muscles. HU increased the glycogen content in all fiber types, and it increased lactate, ATP, and phosphocreatine in the slow type I fiber. After HU, the type I fiber substrate profile was shifted toward that observed in fast fibers. For example, fiber glycogen increased from 179 +/- 16 to 285 +/- 25 mmol/kg dry wt, which approached the 308 +/- 23 mmol/kg dry wt content observed in the post-HU type IIa fiber. With contractile activity, the type I fiber from the HU animal showed a greater utilization of glycogen and accumulation of lactate compared with the control type I fiber. HU had no effect on the ability of crude homogenate or mitochondria fractions from the soleus or gastrocnemius to oxidize pyruvate or palmitate. The increased fatigability after HU may have resulted from an elevated glycolysis producing an increased cell lactate and a decreased pH.

Decreased thin filament density and length in human atrophic soleus muscle fibers after spaceflight.

Soleus muscle fibers were examined electron microscopically from pre- and postflight biopsies of four astronauts orbited for 17 days during the Life and Microgravity Sciences Spacelab Mission (June 1996). Myofilament density and spacing were normalized to a 2. 4-microm sarcomere length. Thick filament density ( approximately 1, 062 filaments/microm(2)) and spacing ( approximately 32.5 nm) were unchanged by spaceflight. Preflight thin filament density (2, 976/microm(2)) decreased significantly (P < 0.01) to 2,215/microm(2) in the overlap A band region as a result of a 17% filament loss and a 9% increase in short filaments. Normal fibers had 13% short thin filaments. The 26% decrease in thin filaments is consistent with preliminary findings of a 14% increase in the myosin-to-actin ratio. Lower thin filament density was calculated to increase thick-to-thin filament spacing in vivo from 17 to 23 nm. Decreased density is postulated to promote earlier cross-bridge detachment and faster contraction velocity. Atrophic fibers may be more susceptible to sarcomere reloading damage, because force per thin filament is estimated to increase by 23%.