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

Abstract

Debold, E. P., H. Dave, and R. H. Fitts. Fiber type and temperature dependence of inorganic phosphate: implications for fatigue. Am J Physiol Cell Physiol 287: C673-C681, 2004. First published May 5, 2004; 10.1152/ajpcell.00044.2004.-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 (Յ15°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°C) and high (30°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 2ϩ levels depressed maximum isometric force (Po) by 54% at 15°C and by 19% at 30°C (P Ͻ 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°C but by only 16% at 30°C in type I fibers. Similarly, in type II fibers, peak power was depressed by 40 and 18% at 15 and 30°C, respectively. These data suggest that near physiological temperatures and at saturating levels of intracellular Ca 2ϩ , elevated levels of Pi contribute less to fatigue than might be inferred from data obtained at lower temperatures. skinned single fiber; force; power REPEATED HIGH-FREQUENCY STIMULATION of muscle results in a rapid decline in muscular force and power, with the degree of change dependent on the duration and intensity of activity as well as on the fiber type composition of the muscle (2, 17). The decline in force has been demonstrated to strongly correlate with an increase in muscle P i concentration (7,44,50). Although the strength of the correlation varies (1), in the later stages of fatigue, when maximal isometric force is depressed by Ͼ70%, the intracellular P i concentration can exceed 30 mM compared with the 1-5 mM level in resting fibers (44). These observations suggest that P i may play a causative role in fatigue.Skinned single muscle fiber studies provide convincing evidence that elevations in P i depress maximum isometric force (P o ) in a concentration-dependent manner (9 -11, 18, 28, 30 -32, 38). Notably, Potma et al. (38) observed a 55% decline in P o after increasing P i from 0 to 30 mM at 15°C in chemically skinned rabbit soleus fibers. Even larger P i -induced reductions in P o were observed in psoas myofibrils (43) and in single fibers when the initial P i concentration was reduced to ϳ5 m with the use of a P i mopping enzyme system (36). High levels of P i are thought to reduce force by reversing the P i release/force-generating step by mass act...

Muscle Fatigue Increases the Probability of Developing Hyperalgesia in Mice

“…Peripherally, fatiguing exercise can result in changes in the muscle tissue that includes increases in lactate, phosphate and creatinine kinase, decreases in pH, and infiltration of neutrophils. 2,8,11,30 Changes in these substances could directly activate nociceptors through acid sensing ion channels and increased release of cytokines and prostaglandins. 5,22,27,31,42,43,47 Alternatively, there could be changes in the buffering capacity of the muscle to maintain pH such that a pH of 5 is buffered slower than under nonfatigue conditions.…”

“…Eccentric induced soreness is generally associated with inflammatory changes in exercised muscle that includes infiltration of leukocytes, increases in lactate, increases in phosphate, fatigue, and pain. 2,8,11,30 In human subjects with experimental muscle pain, there is a decrease in muscle peak force and endurance in painful and in synergistic muscles. 7 A low-intensity, 60-minuteduration tooth clenching task produces fatigue and pain during the task, 49 suggesting fatigue produces pain.…”

Critical temperatures in the cephalopodSepia officinalisinvestigated usingin vivo31P NMR spectroscopy

“…Increased [P i ] is thought to reduce muscle force by reversing the force-generating P i release step by mass action (Hibberd et al, 1985). According to Debold et al (rat muscle fibres), the [P i ] dependency of muscle fatigue is temperature related, with a more pronounced effect of [P i ] at low temperatures (Debold et al, 2004). For ectothermic (marine) animals such studies have, to our knowledge, not been undertaken.…”

Muscle Fatigue from the Perspective of a Single Crossbridge

“…10,18,95 Subsequent experiments that exposed skinned single muscle fibers to fatiguing concentrations of Pi (~30 mM) and H + (pH 6.2 to 6.5) showed that these ions dramatically reduce maximal isometric force, 15,38,61 unloaded shortening velocity, 13 and peak power, 24,46,58 providing strong evidence that these ions play a causative role in the fatigue process. More specifically, because these experiments were , and thus with a fully activated thin filament, it suggests that these depressive effects are due, in part, to a direct effect on the actomyosin crossbridge.…”

“…23,28 In addition, parallel advancements in single muscle fiber technology and transgenic manipulation of the contractile proteins are also providing important new insights into the molecular basis of the fatigue process. 20,24,26,46,[58][59][60] Characterizing the mechanisms of fatigue at the cellular and molecular levels is important because many of the most promising therapeutic interventions act at this level to attenuate the debilitating effects of fatigue in clinical populations. 30, 51,57,74,87 In addition to directly inhibiting the crossbridge cycle, the metabolic by-products that are elevated during intense contractile activity are thought to indirectly affect contractile function by altering the ability of the muscle regulatory proteins (troponin [Tn] and tropomyosin [Tm]) to regulate actomyosin binding by making the thin filament less sensitive to Ca 2+ .…”