Soleus biopsies were obtained from four male astronauts 45 days before and within 2 h after a 17 day spaceflight. For all astronauts, single chemically skinned post‐flight fibres expressing only type I myosin heavy chain (MHC) developed less average peak Ca2+ activated force (Po) during fixed‐end contractions (0.78 ± 0.02 vs. 0.99 ± 0.03 mN) and shortened at a greater mean velocity during unloaded contractions (Vo) (0.83 ± 0.02 vs. 0.64 ± 0.02 fibre lengths s−1) than pre‐flight type I fibres. The flight‐induced decline in absolute Po was attributed to reductions in fibre diameter and/or Po per fibre cross‐sectional area. Fibres from the astronaut who experienced the greatest relative loss of peak force also displayed a reduction in Ca2+ sensitivity. The elevated Vo of the post‐flight slow type I fibres could not be explained by alterations in myosin heavy or light chain composition. One alternative possibility is that the elevated Vo resulted from an increased myofilament lattice spacing. This hypothesis was supported by electron micrographic analysis demonstrating a reduction in thin filament density post‐flight. Post‐flight fibres shortened at 30 % higher velocities than pre‐flight fibres at external loads associated with peak power output. This increase in shortening velocity either reduced (2 astronauts) or prevented (2 astronauts) a post‐flight loss in fibre absolute peak power (μN (fibre length) s−1). The changes in soleus fibre diameter and function following spaceflight were similar to those observed after 17 days of bed rest. Although in‐flight exercise countermeasures probably reduced the effects of microgravity, the results support the idea that ground‐based bed rest can serve as a model of human spaceflight. In conclusion, 17 days of spaceflight decreased force and increased shortening velocity of single Ca2+‐activated muscle cells expressing type I MHC. The increase in shortening velocity greatly reduced the impact that impaired force production had on absolute peak power.

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 purpose of this study was to examine the effect of prolonged bed rest (BR) on the peak isometric force (Po) and unloaded shortening velocity ( V o) of single Ca2+-activated muscle fibers. Soleus muscle biopsies were obtained from eight adult males before and after 17 days of 6° head-down BR. Chemically permeabilized single fiber segments were mounted between a force transducer and position motor, activated with saturating levels of Ca2+, and subjected to slack length steps. V owas determined by plotting the time for force redevelopment vs. the slack step distance. Gel electrophoresis revealed that 96% of the pre- and 87% of the post-BR fibers studied expressed only the slow type I myosin heavy chain isoform. Fibers with diameter >100 μm made up only 14% of this post-BR type I population compared with 33% of the pre-BR type I population. Consequently, the post-BR type I fibers ( n = 147) were, on average, 5% smaller in diameter than the pre-BR type I fibers ( n = 218) and produced 13% less absolute Po. BR had no overall effect on Po per fiber cross-sectional area (Po/CSA), even though half of the subjects displayed a decline of 9–12% in Po/CSA after BR. Type I fiber V oincreased by an average of 34% with BR. Although the ratio of myosin light chain 3 to myosin light chain 2 also rose with BR, there was no correlation between this ratio and V o for either the pre- or post-BR fibers. In separate fibers obtained from the original biopsies, quantitative electron microscopy revealed a 20–24% decrease in thin filament density, with no change in thick filament density. These results raise the possibility that alterations in the geometric relationships between thin and thick filaments may be at least partially responsible for the elevated V o of the post-BR type I fibers.

. The depressive effect of P i on the force-pCa relationship in skinned single muscle fibers is temperature dependent. Am J Physiol Cell Physiol 290: C1041-C1050, 2006. First published November 9, 2005 doi:10.1152/ajpcell.00342.2005.-Increases in P i combined with decreases in myoplasmic Ca 2ϩ 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 Pi on the force-Ca 2ϩ relationship of chemically skinned single muscle fibers at near-physiological temperature (30°C). Fibers isolated from rat soleus (slow) and gastrocnemius (fast) muscle were subjected to a series of solutions with an increasing free Ca 2ϩ concentration in the presence and absence of 30 mM Pi at both low (15°C) and high (30°C) temperature. In slow fibers, 30 mM P i significantly increased the Ca 2ϩ 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°C but was significantly increased at 30°C. At both low and high temperatures, 30 mM P i increased the Ca 2ϩ required to elicit half-maximal force (pCa50) 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 2ϩ and increases in Pi 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 2ϩ levels.force-pCa relationship; phosphate; fatigue HIGH-FREQUENCY STIMULATION of skeletal muscle results in a rapid loss of force and power, with the steepest decline occurring during the later stages of fatigue. This is attributed, at least in part, to elevated levels of P i resulting from the rapid breakdown of ATP and creatine phosphate. In addition, decreases in the intracellular levels of Ca 2ϩ as a result of compromised Ca 2ϩ release also act to reduce force and power (1,2,20). Changes in these ions also may act synergistically to produce even further reductions in force.During intense muscle contraction, a strong inverse correlation exists between muscular force and P i , an observation that supports the hypothesis that increases in intracellular P i at least in part induce fatigue (20,52). This hypothesis stemmed from experiments in single skinned fibers demonstrating that elevated P i reduces isometric force in nonexercised fibers at saturating Ca 2ϩ concentrations (7-9, 36, 38, 39, 42). At a typical fatiguing concentration of 30 mM P i , maximal isometric force (P o ) can be depressed by Ͼ50% compared with near-zero P i in single mammalian fibers (44).In addition to changes in P i , myoplasmic free Ca 2ϩ concentration declines during fatigue, resulting from a decrease in the amount of Ca 2ϩ released from the ...

Soleus muscle fibers from the rat display a reduction in peak power and Ca2+ sensitivity after hindlimb suspension. To examine human responses to non-weight bearing, we obtained soleus biopsies from eight adult men before and immediately after 17 days of bed rest (BR). Single chemically skinned fibers were mounted between a force transducer and a servo-controlled position motor and activated with maximal (isotonic properties) and/or submaximal (Ca2+ sensitivity) levels of free Ca2+. Gel electrophoresis indicated that all pre- and post-BR fibers expressed type I myosin heavy chain. Post-BR fibers obtained from one subject displayed increases in peak power and Ca2+ sensitivity. In contrast, post-BR fibers obtained from the seven remaining subjects showed an average 11% reduction in peak power (P < 0.05), with each individual displaying a 7-27% reduction in this variable. Post-BR fibers from these subjects were smaller in diameter and produced 21% less force at the shortening velocity associated with peak power. However, the shortening velocity at peak power output was elevated 13% in the post-BR fibers, which partially compensated for their lower force. Post-BR fibers from these same seven subjects also displayed a reduced sensitivity to free Ca2+ (P < 0.05). These results indicate that the reduced functional capacity of human lower limb extensor muscles after BR may be in part caused by alterations in the cross-bridge mechanisms of contraction.