Summary ATP provides the energy in our muscles to generate force, through its use by myosin ATPases, and helps to terminate contraction by pumping Ca 2+ back into the sarcoplasmic reticulum, achieved by Ca 2+ ATPase. The capacity to use ATP through these mechanisms is sufficiently high enough so that muscles could quickly deplete ATP. However, this potentially catastrophic depletion is avoided. It has been proposed that ATP is preserved not only by the control of metabolic pathways providing ATP but also by the regulation of the processes that use ATP. Considering that contraction (i.e. myosin ATPase activity) is triggered by release of Ca 2+ , the use of ATP can be attenuated by decreasing Ca 2+ release within each cell. A lower level of Ca 2+ release can be accomplished by control of membrane potential and by direct regulation of the ryanodine receptor (RyR, the Ca 2+ release channel in the terminal cisternae). These highly redundant control mechanisms provide an effective means by which ATP can be preserved at the cellular level, avoiding metabolic catastrophe. This Commentary will review some of the known mechanisms by which this regulation of Ca 2+ release and contractile response is achieved, demonstrating that skeletal muscle fatigue is a consequence of attenuation of contractile activation; a process that allows avoidance of metabolic catastrophe.Key words: Endurance, Membrane excitability, Skeletal muscle contraction Introduction Typically, when exercise scientists think of control of skeletal muscle contraction, they consider motor unit recruitment and rate coding, the primary means by which the brain regulates the magnitude of muscle contraction. However, the magnitude of skeletal muscle contraction can also be regulated at the cellular level. This level of control is necessary to avoid cellular metabolic catastrophe, i.e. the situation in which ATP depletion reaches a level that is damaging to the fiber.ATP is the common final source for energy in the cell, and its concentration [along with the concentrations of ADP and inorganic phosphate (Pi)] affects the magnitude of energy that is made available from its hydrolysis. At rest, skeletal muscle has a low metabolic rate, not unlike many other passive tissues, and the intracellular concentration of ATP is in the 5-7 mM range (Hochachka and Matheson, 1992). However, during muscle activity, there are three major ATPases that require ATP for their function (Box 1); during exercise, skeletal muscle can increase its rate of ATP use by more than 100 times (Hochachka and McClelland, 1997), a rate that is much faster than can be replenished by aerobic metabolism. This latter point is clear from the fact that the muscle power output can greatly exceed the level that can be supported by aerobic metabolism (MacIntosh et al., 2000). To accommodate this additional energy requirement, ATP is provided by non-aerobic means (through phosphocreatine hydrolysis and glycolysis resulting in lactate formation), but this alternative source of ATP has limited capacity (Monod ...
The innovative cycling ergometer is a reliable tool to assess NMF during and immediately postexercise. This will allow fatigue etiology during dynamic exercise with large muscle mass to be revisited in various populations and environmental conditions.
Skeletal muscle contraction is initiated when an action potential triggers the release of Ca2+ into the sarcomere in a process referred to as excitation-contraction coupling. The speed and scale of this process makes direct observation very challenging and invasive. To determine how the concentration of Ca2+ changes within the myofibril during a single activation, several simulation models have been developed. These models follow a common pattern; divide the half sarcomere into a series of compartments, then use ordinary differential equations to solve reactions occurring within and between the compartments. To further develop this type of simulation, we have created a realistic structural model of a skeletal muscle myofibrillar half-sarcomere using MCell software that incorporates the myofilament lattice structure. Using this simulation model, we were successful in reproducing the averaged calcium transient during a single activation consistent with both the experimental and previous simulation results. In addition, our simulation demonstrated that the inclusion of the myofilament lattice within our model produced an asymmetric distribution of Ca2+, with more Ca2+ accumulating near the Z-disk and less Ca2+ reaching the m-line. This asymmetric distribution of Ca2+ is also apparent when we examine how the Ca2+ are bound to the troponin-C proteins along the actin filaments. Our simulation model also allowed us to produce advanced visualizations of this process, including two simulation animations, allowing us to view Ca2+ release, diffusion, binding and uptake within the myofibrillar half-sarcomere.
There are many circumstances where it is desirable to obtain the contractile response of skeletal muscle under physiological circumstances: normal circulation, intact whole muscle, at body temperature. This includes the study of contractile responses like posttetanic potentiation, staircase and fatigue. Furthermore, the consequences of disease, disuse, injury, training and drug treatment can be of interest. This video demonstrates appropriate procedures to set up and use this valuable muscle preparation.To set up this preparation, the animal must be anesthetized, and the medial gastrocnemius muscle is surgically isolated, with the origin intact. Care must be taken to maintain the blood and nerve supplies. A long section of the sciatic nerve is cleared of connective tissue, and severed proximally. All branches of the distal stump that do not innervate the medial gastrocnemius muscle are severed. The distal nerve stump is inserted into a cuff lined with stainless steel stimulating wires. The calcaneus is severed, leaving a small piece of bone still attached to the Achilles tendon. Sonometric crystals and/or electrodes for electromyography can be inserted. Immobilization by metal probes in the femur and tibia prevents movement of the muscle origin. The Achilles tendon is attached to the force transducer and the loosened skin is pulled up at the sides to form a container that is filled with warmed paraffin oil. The oil distributes heat evenly and minimizes evaporative heat loss. A heat lamp is directed on the muscle, and the muscle and rat are allowed to warm up to 37°C. While it is warming, maximal voltage and optimal length can be determined. These are important initial conditions for any experiment on intact whole muscle. The experiment may include determination of standard contractile properties, like the force-frequency relationship, force-length relationship, and force-velocity relationship.With care in surgical isolation, immobilization of the origin of the muscle and alignment of the muscle-tendon unit with the force transducer, and proper data analysis, high quality measurements can be obtained with this muscle preparation.
Journal of Applied Physiology Viewpoint on the 2-h marathon barrier (3). We would argue that, alongside having a superlative V O 2max , lactate threshold, and running economy, it will be required for this athlete to have an individualized and aggressive fueling strategy coupled with a predisposition for high exogenous CHO oxidation (CHO exog ), without a history of GI distress. It is clear that supplemented carbohydrate (CHO) improves prolonged endurance performance (Ͼ90 min) compared with water (2). Furthermore, recent evidence has demonstrated a positive dose-response relationship between supplemented CHO, CHO exog , and endurance performance; where 60 g CHO/h outperformed either 15 or 30 g CHO/h (5). The maximal CHO exog with single CHO sources appears to be ϳ1 g/min due to limitations of the intestinal transporters (1). However, despite any individual differences in CHO exog or history of GI distress (4), CHO exog is not dependent on body weight (BW), as a recent analysis has shown no relationship between BW and CHO exog (1). Accordingly, a 56-kg runner is able to oxidize ϳ20% more per kg BW compared with a 70-kg runner with a given CHO exog rate of ϳ1 g/min (1.07 vs.0.86 g CHO·h Ϫ1 ·kg BW Ϫ1 ). Therefore, there appears to be a distinct CHO exog advantage for lighter marathon runners compared with heavier. Thus the future 2-h marathon runner will feature a low BW, both for improved thermoregulation, but also optimal CHO exog per kg BW. All of these elements will need to be possessed by the first athlete to break the 2-h marathon barrier. TO THE EDITOR: In their Viewpoint, Joyner, Ruiz, and Lucia (2) specifically highlight the important role of "exceptional running economy" as one of the main physiological factors for breaking 2 h for a marathon run. We totally agree that future studies should investigate not only mechanical factors related to running economy, but also the complex links between heat storage, body size, and functional links between muscle and brain with fatigue. First, as a plausible source of "exceptional running economy" there are some favorable types of runner's footstrike patterns. Recent detailed analyses of foot kinematics and kinetics in barefoot and shod Kalenjin runners (2) corroborate and extend what is known about the mechanics of barefoot running (3). So, fore-foot striking runners are prompt to take further advantage of elastic energy storage in both the Achilles tendon and the longitudinal arch of the foot. Second, one possible issue is that athletes (African vs. white runners) pace themselves differently during marathon in hot conditions (4), and the rate of heat storage is a likely candidate that mediates this difference. Part of this difference is the larger body size of the white runners, suggesting that their rate of heat storage would be higher than the African runners at the same speed. Third, the breakdown of running style over the distance suggests that muscles are no longer activated ideally and ultimately central nervous system is affected by long-lasting exercise (...
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