Cause Of Muscle Fatigue Research Articles

The Effects of Aerobic Sports on Fatigue and Vital Sign in Sportsman

The lactic acid buildup has long been suspected as a cause of muscle fatigue. Lactate is a waste of anaerobic metabolism; this process takes place in the absence of oxygen. Blood pressure, pulse, and respiration are vital signs to monitor adaptation to fatigue levels. This study aims to determine the effect of aerobic exercise on the level of fatigue and vital signs in athletes. This research is a quasi-experimental study with a non-random re-experimental design. Lactic acid levels and vital signs were assessed before and after the exercise program in 3 groups, namely the light-intensity exercise treatment group, the moderate-intensity exercise group, and the control group. The research site is at the Harapan Bangsa football stadium in Banda Aceh. The subject of PPLP Dispora Aceh athletes. The exercise was carried out for four weeks. The average lactic acid levels of the three groups showed differences. A significant decrease in lactic acid after the training test was seen in the group with OAIS (p = 0.04). Exercise with the right intensity, duration, and frequency can reduce lactic acid levels and vital signs. This study shows that moderate-intensity exercise can affect reducing lactic acid levels and vital signs so that it can slow down fatigue during exercise in Aceh football athletes. Keywords: Light and Moderate Intensity Exercise, Lactic Acid, Vital Signs.

Can Proprioceptive Training Reduce Muscle Fatigue in Patients With Motor Neuron Diseases? A New Direction of Treatment.

Muscle fatigue is a serious problem in patients with motor neuron diseases (MNDs). It commonly disturbs both daily life activity and rehabilitation tolerance. A particular concern should be taken when MNDs occur in older ages. Older patients with MNDs usually have a worse clinical presentation and a lower survival rate. This could increase the occurrence of muscle fatigue. Muscle fatigue occurs due to a dysfunction in either motor or sensory systems. Current exercise interventions performed to decrease the occurrence of muscle fatigue focused only on treating motor causes of muscle fatigue. It has been demonstrated that these interventions have a high debate in their effectiveness on decreasing the occurrence of muscle fatigue. Also, these exercise interventions ignored training the affected sensory part of muscle fatigue, however, the important role of the sensory system in driving the motor system. Thus, this review aimed to develop a novel exercise intervention by using proprioceptive training as an intervention to decrease the occurrence of muscle fatigue in patients with MNDs particularly, older ones. The physiological effects of proprioceptive training to decrease the occurrence of muscle fatigue could include two effects. The first effect includes the ability of the proprioceptive training to increase the sensitivity of muscle spindles as an attempt to normalize the firing rate of α-motoneurons, which their abnormalities have major roles in the occurrence of muscle fatigue. The second effect includes its ability to correct the abnormal movement-compensations, which develop due to the biomechanical constraints imposed on patients with MNDs.

C2C12 근아세포의 산화적 손상에 대한 고삼, 감초 및 백선피 복합 추출물의 보호효과

Objectives : Increased oxidative stress by reactive oxygen species (ROS) has been suggested as a major cause of muscle fatigue. Although several studies have demonstrated the various biological properties of Sophora flavescens Aiton, Glycyrrhiza uralensis Fischer and Dictamnus dasycarpus Turcz, but the antioxidative potentials have not been clearly demonstrated. The present study was designed to investigate the protective effects of their water and ethanol extract mixtures (medicinal herbal mixtures, MHMIXs) on hydrogen peroxide (<TEX>$H_2O_2$</TEX>)-induced cell damage and apoptosis in C2C12 myoblasts. Methods : Cytotoxicity was assessed by an MTT assay. Quantitative evaluation of apoptosis induction and ROS production was evaluated by flow cytometry analysis. Expression levels of apoptosis regulatory and DNA-damage proteins were detected by Western blotting. Result : The inhibition of <TEX>$H_2O_2$</TEX>-induced cell proliferation was effectively blocked in extracts of 3: 1: 1 (EMHMIXs-1) or 2: 2: 1 (EMHMIXs-2) of S. flavescens, G. uralensis and D. dasycarpus Turcz, ethanol extracts from various complex extracts in C2C12 myoblasts. EMHMIXs-1 and EMHMIXs-2 also effectively attenuated <TEX>$H_2O_2$</TEX>-induced C2C12 cell apoptosis, which was associated with the restoration of the upregulation of Bad and death receptor 4, and downregulation of XIAP and cIAP-1 induced by <TEX>$H_2O_2$</TEX>. In addition, these herbal mixtures significantly blocked the <TEX>$H_2O_2$</TEX>-induced ROS generation and phosphorylation of <TEX>$p-{\gamma}H2A.X$</TEX>, which suggests that they can prevent <TEX>$H_2O_2$</TEX>-induced cellular DNA damage. Conclusions : The results suggest that EMHMIXs-1 and EMHMIXs-2 could block the DAN damage and apoptosis of C2C12 myoblasts by oxidative stress through blocking ROS generation.

Excitation of skeletal muscle is a self-limiting process, due to run-down of Na+, K+ gradients, recoverable by stimulation of the Na+, K+ pumps.

The general working hypothesis of this study was that muscle fatigue and force recovery depend on passive and active fluxes of Na+ and K+. This is tested by examining the time-course of excitation-induced fluxes of Na+ and K+ during 5–300 sec of 10–60 Hz continuous electrical stimulation in rat extensor digitorum longus (EDL) muscles in vitro and in vivo using 22Na and flame photometric determination of Na+ and K+. 60 sec of 60 Hz stimulation rapidly increases 22Na influx, during the initial phase (0–15 sec) by 0.53 μmol(sec)−1(g wet wt.)−1, sixfold faster than in the later phase (15–60 sec). These values agree with flame photometric measurements of Na+ content. The progressive reduction in the rate of excitation-induced Na+ uptake is likely to reflect gradual loss of excitability due to accumulation of K+ in the extracellular space and t-tubules leading to depolarization. This is in keeping with the concomitant progressive loss of contractile force previously demonstrated. During electrical stimulation rat muscles rapidly reach high rates of active Na+, K+-transport (in EDL muscles a sevenfold increase and in soleus muscles a 22-fold increase), allowing efficient and selective compensation for the large excitation-induced passive Na+, K+-fluxes demonstrated over the latest decades. The excitation-induced changes in passive fluxes of Na+ and K+ are both clearly larger than previously observed. The excitation-induced reduction in [Na+]o contributes considerably to the inhibitory effect of elevated [K+]o. In conclusion, excitation-induced passive and active Na+ and K+ fluxes are important causes of muscle fatigue and force recovery, respectively.

PGC-1α mediates a rapid, exercise-induced downregulation of glycogenolysis in rat skeletal muscle.

Long-term endurance exercise training results in a reduction in the rates of muscle glycogen depletion and lactic acid accumulation during submaximal exercise; this adaptation is mediated by an increase in muscle mitochondria. There is evidence suggesting that short-term training induces adaptations that downregulate glycogenolysis before there is an increase in functional mitochondria. We discovered that a single long bout of exercise induces decreases in expression of glycogenolytic and glycolytic enzymes in rat skeletal muscle; this adaptation results in slower rates of glycogenolysis and lactic acid accumulation in muscle during contractile activity. Two additional days of training amplified the adaptive response, which appears to be mediated by PGC-1α; this adaptation is biologically significant, because glycogen depletion and lactic acid accumulation are major causes of muscle fatigue. Endurance exercise training can increase the ability to perform prolonged strenuous exercise. The major adaptation responsible for this increase in endurance is an increase in muscle mitochondria. This adaptation occurs too slowly to provide a survival advantage when there is a sudden change in environment that necessitates prolonged exercise. In the present study, we discovered another, more rapid adaptation, a downregulation of expression of the glycogenolytic and glycolytic enzymes in muscle that mediates a slowing of muscle glycogen depletion and lactic acid accumulation. This adaptation, which appears to be mediated by PGC-1α, occurs in response to a single exercise bout and is further enhanced by two additional daily exercise bouts. It is biologically significant, because glycogen depletion and lactic acid accumulation are two of the major causes of muscle fatigue and exhaustion.

Pharmacologic Treatment of Downstream of Tyrosine Kinase 7 Congenital Myasthenic Syndrome

Congenital myasthenic syndromes (CMSs) are increasingly recognized as causes of muscle fatigue and weakness. However, treatment of individual syndromes has been described only in small case series. To analyze the information published thus far concerning the effect of pharmacologic treatment of one of the most common subtypes of CMS, downstream of tyrosine kinase 7 (DOK7) CMS. In a search of the PubMed database, we found 16 publications describing the response to medication in 122 individuals with DOK7 deficiency. The last search was performed August 15, 2013. If more than 1 article had been published by the same group, a comparison of the participants in the studies was made, and data appearing more than once were excluded. Positive effects were observed in 6 of 66 patients who received an acetylcholinesterase inhibitor, 65 of 69 patients who received ephedrine or salbutamol, 18 of 29 who were given 3,4-diaminopyridine, and 13 of 16 individuals who received a combination of these drugs. Our analysis found no evidence that age at disease onset, age at treatment start, drug dosage, or mutation type influenced treatment results. The magnitude of treatment effect with ephedrine or salbutamol seems to increase gradually, peaking after approximately 6 to 8 months. Treatment with acetylcholinesterase inhibitors resulted in worsened conditions for most patients. This analysis suggests that (1) ephedrine or salbutamol is the first choice of treatment in DOK7 CMS; (2) 3,4-diaminopyridine may provide additional benefi; (3) it is never too late to initiate treatment; and (4) in contrast to acquired myasthenia gravis, treatment with acetylcholinesterase inhibitors should be avoided in DOK7 CMS.

C2C12 근육세포의 산화적 손상에 대한 홍경천-홍삼 추출물 혼합액 발효물의 보호효과

본 연구에서는 피로 회복 또는 원기 회복에 효능이 있는 것으로 알려진 홍경천과 홍삼을 이용하여 홍경천-홍삼 복합 발효물의 산화적 손상 억제 효과를 평가하고자 <TEX>$H_2O_2$</TEX>로 산화적 스트레스를 유도시킨 C2C12 근육세포에 홍경천-홍삼 복합 발효물의 처리한 후, 세포의 morphology, cell viability 및 항산화 효소들의 유전자 발현 양상을 비교, 분석하였다. 홍경천-홍삼 복합 발효물은 C2C12 근육세포의 cell viability를 유의적으로 증가시켰으며, Cu/Zn-SOD, Mn-SOD 및 GPx 등과 같은 세포내 항산화 효소의 발현을 증가시킬 뿐만 아니라, 근육세포 분화의 주요 전사인자인 Myo D의 발현 또한 증가시키는 것으로 나타났다. 이상의 결과로, 홍경천-홍삼 복합 발효물은 세포내 항산화 효소 시스템을 증가시켜 외부로부터의 산화적 손상에 대한 방어효능을 갖는 것으로 나타났으며, 향후 in vivo 시스템 이용한 추가적인 연구가 수행된다면, 홍경천-홍삼 복합 발효물을 이용한 항피로 건강기능식품의 소재개발이 가능할 것으로 판단된다. Rhodiola spp. and red ginseng have been used for food and medicinal applications in disease chemoprevention in many Asian countries. Increased oxidative stress by reactive oxygen species (ROS) has been proposed to be a major cause of muscle fatigue. The present study was designed to investigate the protective effects of a fermented hot-water extract mixture from Rhodiola sachalinensis and red ginseng (MFR) on cell damage and the antioxidant enzyme system in <TEX>$H_2O_2$</TEX>-induced oxidative stress in skeletal muscle cells. C2C12 myoblasts were treated with various concentrations of NFR (non-fermented Rhodiola sachalinensis extract), FR (fermented hot-water extract from Rhodiola sachalinensis) and MFR for up to 5 days after the standard induction of differentiation, followed by semi-quantitative RT-PCR. MFR treatment dose-dependently protected oxidative damage of C2C12 cells. The treatment with MFR also enhanced mRNA expressions of MyoD, Cu/Zn SOD, Mn-SOD and GPX up to 16%. These results indicate that MFR exerts an anti-oxidative effect through a mechanism (s) that may involve the up-regulation of antioxidant enzymes, which may be important for the cellular redox environment in muscle cells.

Quantification of Na+,K+ pumps and their transport rate in skeletal muscle: Functional significance

During excitation, muscle cells gain Na+ and lose K+, leading to a rise in extracellular K+ ([K+]o), depolarization, and loss of excitability. Recent studies support the idea that these events are important causes of muscle fatigue and that full use of the Na+,K+-ATPase (also known as the Na+,K+ pump) is often essential for adequate clearance of extracellular K+. As a result of their electrogenic action, Na+,K+ pumps also help reverse depolarization arising during excitation, hyperkalemia, and anoxia, or from cell damage resulting from exercise, rhabdomyolysis, or muscle diseases. The ability to evaluate Na+,K+-pump function and the capacity of the Na+,K+ pumps to fill these needs require quantification of the total content of Na+,K+ pumps in skeletal muscle. Inhibition of Na+,K+-pump activity, or a decrease in their content, reduces muscle contractility. Conversely, stimulation of the Na+,K+-pump transport rate or increasing the content of Na+,K+ pumps enhances muscle excitability and contractility. Measurements of [3H]ouabain binding to skeletal muscle in vivo or in vitro have enabled the reproducible quantification of the total content of Na+,K+ pumps in molar units in various animal species, and in both healthy people and individuals with various diseases. In contrast, measurements of 3-O-methylfluorescein phosphatase activity associated with the Na+,K+-ATPase may show inconsistent results. Measurements of Na+ and K+ fluxes in intact isolated muscles show that, after Na+ loading or intense excitation, all the Na+,K+ pumps are functional, allowing calculation of the maximum Na+,K+-pumping capacity, expressed in molar units/g muscle/min. The activity and content of Na+,K+ pumps are regulated by exercise, inactivity, K+ deficiency, fasting, age, and several hormones and pharmaceuticals. Studies on the α-subunit isoforms of the Na+,K+-ATPase have detected a relative increase in their number in response to exercise and the glucocorticoid dexamethasone but have not involved their quantification in molar units. Determination of ATPase activity in homogenates and plasma membranes obtained from muscle has shown ouabain-suppressible stimulatory effects of Na+ and K+.

Excitation-induced exchange of Na+, K+, and Cl- in rat EDL muscle in vitro and in vivo: physiology and pathophysiology.

In skeletal muscle, excitation leads to increased [Na+]i, loss of K+, increased [K+]o, depolarization, and Cl− influx. This study quantifies these changes in rat extensor digitorum longus (EDL) muscles in vitro and in vivo using flame photometric determination of Na+ and K+ and 36Cl as a tracer for Cl−. In vitro, 5-Hz stimulation for 300 s increased intracellular Na+ content by 4.6 ± 1.2 µmol/g wet wt (P < 0.002) and decreased intracellular K+ content by 5.5 ± 2.3 µmol/g wet wt (P < 0.03). This would increase [K+]o by 28 ± 12 mM, sufficient to cause severe loss of excitability as the result of inactivation of Na+ channels. In rat EDL, in vivo stimulation at 5 Hz for 300 s or 60 Hz for 60 s induced significant loss of K+ (P < 0.01), sufficient to increase [K+]o by 71 ± 22 mM and 73 ± 15 mM, respectively. In spite of this, excitability may be maintained by the rapid and marked stimulation of the electrogenic Na+,K+ pumps already documented. This may require full utilization of the transport capacity of Na+,K+ pumps, which then becomes a limiting factor for physical performance. In buffer containing 36Cl, depolarization induced by increasing [K+]o to 40–80 mM augmented intracellular 36Cl by 120–399% (P < 0.001). Stimulation for 120–300 s at 5–20 Hz increased intracellular 36Cl by 100–188% (P < 0.001). In rats, Cl− transport in vivo was examined by injecting 36Cl, where electrical stimulation at 5 Hz for 300 s or 60 Hz for 60 s increased 36Cl uptake by 81% (P < 0.001) and 84% (P < 0.001), respectively, indicating excitation-induced depolarization. Cl− influx favors repolarization, improving K+ clearance and maintenance of excitability. In conclusion, excitation-induced fluxes of Na+, K+, and Cl− can be quantified in vivo, providing new evidence that in working muscles, extracellular accumulation of K+ is considerably higher than previously observed and the resulting depression of membrane excitability may be a major cause of muscle fatigue.

An Intermittent Pneumatic Compression Device Reduces Blood Lactate Concentrations More Effectively Than Passive Recovery after Wingate Testing

An Intermittent Pneumatic Compression Device Reduces Blood Lactate Concentrations More Effectively Than Passive Recovery after Wingate Testing With the advancement of technology, therapeutic modalities mimicking “cool down” have become an option for active individuals to try and decrease the recovery time between training sessions and competition. A wide variety of companies that manufacture these modalities have claimed their machines can decrease recovery time by decreasing lactic acid, a known cause of muscle fatigue following exercise. The aim of this study was to investigate an intermittent pneumatic compression (IPC) unit as a recovery modality by evaluating its effectiveness in clearing blood lactate (BLa) when compared to alternate recovery methods following an anaerobic Wingate cycling test (WAnT).

Recent Insights into the Molecular Basis of Muscular Fatigue

The cause of muscle fatigue has been studied for more than 100 yr, yet its molecular basis remains poorly understood. Prevailing theories suggest that much of the fatigue-induced loss in force and velocity can be attributed to the inhibitory action of metabolites, principally phosphate (Pi) and hydrogen ions (H, i.e., acidosis), on the contractile proteins, but the precise detail of how this inhibition occurs has been difficult to visualize at the molecular level. However, recent technological developments in the areas of biophysics, molecular biology, and structural biology are enabling researchers to directly observe the function and dysfunction of muscle contractile proteins at the level of a single molecule. In fact, the first direct evidence that high levels of H and Pi inhibit the function of muscle's molecular motor, myosin, has recently been observed in a single molecule laser trap assay. Likewise, advances in structural biology are taking our understanding further, providing detail at the atomic level of how some metabolites might alter the internal motions of myosin and thereby inhibit its ability to generate force and motion. Finally, new insights are also being gained into the indirect role that muscle regulatory proteins troponin (Tn) and tropomyosin (Tn) play in the fatigue process. In vitro studies, incorporating TnTm, suggest that a significant portion of the decreased force and motion during fatigue may be mediated through a disruption of the molecular motions of specific regions within Tn and Tm. These recent advances are providing unprecedented molecular insight into the structure and function of the contractile proteins and, in the process, are reshaping our understanding of the process of fatigue.

Ergnomic Design of Computer Keyboard Base on the Finger Workspace Analysis

Frequently wiggle of wrists is the primary cause of muscle fatigue and occupational diseases in the computer keyboard operation. It is revealed that the wiggle of wrist is caused by the workspace limit of finger tip. Based on the movement study and workspace analysis for human finger, a new type of computer keyboard designed with ergonomic consideration is put out. A tilting keyboard is used in the new configuration to fit the shape of finger workspace. It was approved by experiment that the new keyboard could reduce the rotation of wrist obviously, therefore to improve the comfort and avoid disorder of the wrist during operation.

Oxidative stress in skeletal muscle causes severe disturbance of exercise activity without muscle atrophy

The increase in reactive oxygen species (ROS) levels that occurs during intense exercise has been proposed to be one of the major causes of muscle fatigue. In addition, the accumulation of cellular damage due to ROS is widely regarded to be one of the factors triggering age-related pathological conditions in skeletal muscle. To investigate the pathological significance of oxidative stress in skeletal muscle, we generated skeletal muscle-specific manganese superoxide dismutase-deficient (muscle- Sod2 −/−) mice. The mutant mice showed severe disturbances in exercise activity, but no atrophic changes in their skeletal muscles. In histological and histochemical analyses, the mutant mice showed centralized nuclei in their muscle fibers and selective loss of enzymatic activity in mitochondrial respiratory chain complexes. In addition, the mutant mice displayed increased oxidative damage and reduced ATP content in their muscle tissue. Furthermore, a single administration of the antioxidant EUK-8 significantly improved exercise activity and increased the cellular ATP level in skeletal muscle. These results imply that the superoxide anions generated in mitochondria play a pivotal role in the progression of exercise intolerance.

The Fast Skeletal Troponin Activator, CK-1909178 Reduces Muscle Fatigue in a Model of Peripheral Artery Disease in Situ

CK-1909178 is a member of a class of fast skeletal troponin activators that sensitize skinned skeletal muscle fibers to calcium. In rat muscle preparations in vitro and in situ, CK-1909178 increased sub-tetanic force without altering maximum force. Given that a major cause of muscle fatigue during repeated muscle contraction is reduced myoplasmic Ca2+ due to impaired sarcoplasmic reticulum Ca2+ release, we tested whether increased calcium sensitivity with CK-1909178 would slow the development of fatigue. Rat flexor digitorum brevis muscle was pretreated in vitro with CK-1909178 and stimulated every 3 seconds at a frequency sufficient to achieve 50% of maximum force for 6 min at 30°C. CK-1909178 diminished the extent of fatigue as compared to control (terminal force 29.5±8% vs. 12.7±4%, p<0.001). We next tested whether CK-1909178 treatment would slow the development of muscle fatigue using rat extensor digitorum longus muscle in situ, where the muscle was stimulated via the peroneal nerve. To accelerate the development of muscle fatigue, vascular insufficiency was produced by femoral artery ligation (FAL). Muscle fatigue with FAL and sham ligation in the presence and absence of CK-1909178 was assessed. CK-1909178 was administered as a 5mg/kg intravenous bolus before assessment of fatigue at a frequency adjusted to achieve the same force at 30Hz prior to dosing. FAL resulted in significantly reduced terminal tension as compared to sham (33±4% vs. 77±5%, p<0.01). CK-1909178 administration significantly attenuated FAL-induced fatigue at 10 minutes (61±7% vs. 33±4%, p<0.01). In summary, CK-1909178 increased sub-maximal muscle force development and reduced the extent of fatigue in the presence of limited blood flow in situ. We believe that this mechanism may improve muscle fatigue in diseases where blood flow to muscles is compromised such as intermittent claudication.

Effects of Changes in Extracellular Concentration of Na+ and K+ ([Na+]o, [K+]o) on the Ca2+ Release Elicited by High Frequency Stimulation. Implications for Muscle Fatigue

Changes in [Na+]o and [K+]o occurring during high frequency stimulation has been proposed as a cause of muscle fatigue. We investigated this hypothesis by measuring the Ca2+ release elicited by short high frequency trains (100Hz, 10 pulses) in rested frog semitendinosus fibers exposed to various [Na+]o or [K+]o. Myoplasmic [Ca2+] changes (Ca2+ transients) elicited by action potentials (AP) were estimated from Ca2+-dependent OGB-5N fluorescence changes. Segments of fibers, stretched to 4.5-5μm, were mounted in an inverted double grease-gap chamber placed in an inverted microscope equipped for epifluorescence. Fibers were held at -100mV and stimulated with 0.5ms current pulses. Normal Ringer solution contained (mM): 115 NaCl, 2.5 KCl, 1.8 CaCl2, 10 MOPS, 10 dextrose, pH=7.2 with NaOH. [K+]o ([Na+]o) was increased (reduced) by equimolar replacement with Na+ (N-methyl-D-glucamine). Fibers were loaded (30min) with a solution containing (mM): 110 aspartate, 5 ATP-K2, 5 Na2-creatine-phosphate, 20 MOPS, 0.05-0.1 EGTA, 5 MgCl2, 0.2 OGB-5N, pH=7.2 with KOH. A complex interaction of the effects of changing [K+]o or [Na+]o on membrane potential, AP overshoot and duration, and Ca2+ release was found. Using normal Ringer, the amplitude of Ca2+ transients elicited by single pulses increased with depolarizations up to -65mV. Raising [K+]o had a dual effect on Ca2+ release. Ca2+ transient's amplitude increased between 2.5 to 10 mM, and decreased markedly for higher [K]o. Potentiation of Ca2+ release, but not depression, could be reverted by current injection. This suggests a depolarization independent effect of K+ ions on Ca2+ release. Halving [Na+]o did not affect Ca2+ release elicited by single stimulation, but impaired the release in response to repetitive stimulation. Further reduction of [Na+]o to 1/3 of normal highly reduced Ca2+ release.

An elevated sarcolemmal lactate (and proton) transport capacity is an advantage during muscle activity in healthy humans.

The etiology of muscle fatigue remains incompletely solved especially in vivo (3). The causes of muscle fatigue vary according to the type, duration and intensity of exercise, and to the physical fitness and health status of the subjects. Nevertheless, an elevated sarcolemmal lactate (and proton) transport capacity constitutes an advantage during muscle activity. During moderate-intensity exercise, efficient lactate exchanges contribute to the cell-cell lactate shuttle i.e., the delivery of lactate for its utilization as fuel by neighboring or distant active and oxidative muscles fibers or as substrate by other tissues (e.g. for neoglucogenesis by the liver) (1). During high-intensity exercise, the lactate exchange ability was positively correlated with the capacity to prolong exercise (4). Whether this correlation between the lactate exchange ability and performance was (directly or indirectly) causal or coincidental, the question is still under debate. Nevertheless, it remains that an elevated lactate exchange ability seems to constitute a protective mechanism against muscle fatigue. Since the transport of lactate across the sarcolemma is mediated mainly by the lactate-H+ cotransport via the monocarboxylate transporters MCT1 and MCT4, an elevated lactate transport capacity delays both muscle lactate accumulation and intracellular pH decrease and seems to favor muscle activity. In accordance, previous experiments have shown that metabolic alkalosis enhances the net lactate release rate from the active muscles and work capacity (2, 5) contrary to acidosis that reduces lactate efflux from muscle and exercise tolerance (5). All this makes an elevated sarcolemmal lactate (and proton) transport capacity an advantage during muscle activity.

Explaining pH Change in Exercising Muscle: Lactic acid, Proton Consumption, and Buffering vs. Strong Ion Difference

The development of acidosis during intense exercise has traditionally been explained by the increased production of lactic acid, causing the release of a proton and the formation of the acid salt sodium lactate. On the basis of this explanation, if the rate of lactate production is high enough, the cellular proton buffering capacity can be exceeded, resulting in a decrease in cellular pH. These biochemical events have been termed lactic acidosis. The lactic acidosis of exercise has been a classic explanation of the biochemistry of acidosis for more than 80 years. This belief has led to the interpretation that lactate production causes acidosis and, in turn, that increased lactate production is one of the several causes of muscle fatigue during intense exercise. This review presents clear evidence that there is no biochemical support for lactate production causing acidosis. Lactate production retards, not causes, acidosis. Similarly, there is a wealth of research evidence to show that acidosis is caused by reactions other than lactate production. Every time ATP is broken down to ADP and Pi, a proton is released. When the ATP demand of muscle contraction is met by mitochondrial respiration, there is no proton accumulation in the cell, as protons are used by the mitochondria for oxidative phosphorylation and to maintain the proton gradient in the intermembranous space. It is only when the exercise intensity increases beyond steady state that there is a need for greater reliance on ATP regeneration from glycolysis and the phosphagen system. The ATP that is supplied from these nonmitochondrial sources and is eventually used to fuel muscle contraction increases proton release and causes the acidosis of intense exercise. Lactate production increases under these cellular conditions to prevent pyruvate accumulation and supply the NAD+ needed for phase 2 of glycolysis. Thus increased lactate production coincides with cellular acidosis and remains a good indirect marker for cell metabolic conditions that induce metabolic acidosis. If muscle did not produce lactate, acidosis and muscle fatigue would occur more quickly and exercise performance would be severely impaired.

The following letters are in response to Point:Counterpoint series “Lactic acid accumulation is an advantage/disadvantage during muscle activity”

The following letters are in response to Point:Counterpoint series “Lactic acid accumulation is an advantage/disadvantage during muscle activity” that appeared in the April issue ( J Appl Physiol 100: 1410–1414, 2006; ). To the Editor :

高強度運動における筋疲労の要因 : 無機リン酸, グリコーゲンおよび活性酸素種の影響

Skeletal muscles induced to contract repeatedly respond with a progressive loss in their ability to generate a target force or power. This decline in function, referred to as muscle fatigue, has a complex etiology that can involve various metabolic and ionic factors. Of these, intracellular acidosis due to lactic acid accumulation has been regarded as one of the important causes of muscle fatigue that occurs with intense exercise. Recent surveys, however, have demonstrated little direct effect of acidosis on muscle function at physiological temperatures, and in fact several putative mechanisms by which intracellular changes can attenuate contractile function have been proposed. The most likely mechanisms to explain muscle fatigue include elevated inorganic phosphate concentrations that result from phosphocreatine breakdown, compartmentalized depletion of endogenous muscle glycogen and/or modification by reactive oxygen species that are produced extensively in contracting muscle fibers. This brief review seeks to examine how these three alterations contribute to muscular fatigue processes.

Lactate is a metabolic substrate that sustains extraocular muscle function

Lactic acid is considered the end product of glycolysis and is a major cause of muscle fatigue. However, the lactate dehydrogenase (LDH) reaction is bidirectional: Lactate can be oxidized to pyruvate and used as a substrate for the Krebs cycle. Therefore, our hypothesis was that lactate sustains the contractile function of rat extraocular muscles during periods of increased activity. The study used extraocular and extensor digitorum longus (EDL) muscles from adult Sprague-Dawley rats to determine LDH isoform expression, total LDH activity, and contractile function in vitro. To evaluate the role of lactate on fatigue, we tested the effect of cinnamate, a blocker of lactate transport, and exogenous lactate on fatigue resistance. Cinnamate accelerated fatigue in the extraocular muscles: Endurance and residual force decreased significantly. Conversely, cinnamate did not affect the endurance or residual force of EDL muscles. Replacing glucose with exogenous lactate increased EDL fatigability but had no effect on the extraocular muscles. However, the extraocular muscles fatigued faster when exposed to exogenous lactate combined with cinnamate. The LDH-A and LDH-C isoforms were expressed at lower levels in extraocular muscle; LDH-B was equally abundant in the EDL and extraocular muscles. Total LDH activity in the extraocular muscles was only approximately 32% of the level in EDL. These results support the hypothesis that lactate sustains the contractile performance of the extraocular muscles.