Open Access

Monocarboxylate Transporters and Lactate Metabolism in Equine Athletes: A Review

  • AR Pösö1
Acta Veterinaria Scandinavica200243:63

DOI: 10.1186/1751-0147-43-63

Received: 19 November 2001

Accepted: 21 November 2001

Published: 30 June 2002

Abstract

Lactate is known as the end product of anaerobic glycolysis, a pathway that is of key importance during high intensity exercise. Instead of being a waste product lactate is now regarded as a valuable substrate that significantly contributes to the energy production of heart, noncontracting muscles and even brain. The recent cloning of monocarboxylate transporters, a conserved protein family that transports lactate through biological membranes, has given a new insight into the role of lactate in whole body metabolism. This paper reviews current literature on lactate and monocarboxylate transporters with special reference to horses.

Keywords

Horse MCT skeletal muscle Red blood cell Exercise.

Sammanfattning

Monokarboxylat transportörer och laktat metabolismen hos tävlingshästar

Mjölksyra är en känd slutprodukt av den anaeroba glykolysen, en reaktionskedja som är viktig under hårt arbete. Nyligen klonade transportproteiner för monokarboxylsyror, som formar en konserverad protein familj och som transporterar mjölksyra genom biologiska membraner, har givit en ny inblick i mjölksyrans roll i kroppsmetabolismen. Istället för att vara en värdelös slutprodukt anses mjölksyra nu vara ett värdefullt substrat som i väsentlig grad deltar i energiproduktionen i hjärtat, okontraherande muskler och även hjärnan. I den här artikeln refereras ny litteratur om mjölksyra och om monokarboxylsyra transportörer med speciell hänvisning till hästar.

Keywords

Horse MCT skeletal muscle Red blood cell Exercise.

Introduction

Horses are superb athletes in comparison to other athletic species. Exceptionally high maximal oxygen uptake, a splenic reserve of red blood cells released into the circulation during exercise, and a high amount of energy stored as glycogen in the muscles contribute to the high performance capacity of a horse [27, 9]. Furthermore, equine muscles and blood are equipped with properties that increase their tolerance to lactic acid, the formation of which is necessary for maximal performance. The buffer capacity of muscles of trained horses is higher than in other athletic species, and red blood cells appear to function as a lactate sink, both of which phenomena may increase the anaerobic capacity [40, 51]. Because the lactic acid-induced acidification is the single most important factor causing fatigue, the regulation of its concentration in exercising muscle plays a central role in muscle function. Recent characterisation of monocarboxylate transporters, a protein family involved in the transport of lactate across biological membranes, has added a new perspective to our knowledge of lactate metabolism in exercise physiology [50, 21]. At the moment the physiological importance of these transporters is not completely understood, but the number of isoforms of monocarboxylate transporters and the conservative nature of these proteins suggest that the pathways of lactate are far more complex than generally believed.

Formation of lactate in muscle

Formation of lactic acid in muscle tissue is basically a question of the capacity of different metabolic pathways. Both at rest and during exercise, the rate of ADP rephosphorylation must meet the demand of ATP for contraction and other functions of the muscle cell. During light work, the demand for ATP lies within the limits of aerobic capacity, and ATP is produced by oxidative phosphorylation, but with increasing intensity, anaerobic pathways of energy production, i.e., substrate-level phosphorylation, become more important. It has been calculated that during a 400-m Quarter Horse race, about 60% of the energy is derived from anaerobic metabolism, and in longer races, such as in1600- to 2100-m Thoroughbred and Standardbred races, estimated values range from 10% to 30% [13].

Aerobic capacity varies among breeds of horses, among muscles and also among fiber types. Slow-twitch, type I, fibers usually have higher aerobic capacity than the fast-twitch, especially type IIB, fibers, which usually rely more on the anaerobic metabolism [41]. The characteristics of type IIB fibers are species specific and also depend on training. For example, in reindeer and in well trained horses also type IIB fibers have high oxidative capacity [55, 52]. Availability of oxygen and the capacity to use it are the limiting factors for aerobic metabolism. This includes the cardio-respiratory function, hemoglobin concentration in the blood, transit time of the blood in the muscle, capillarization, myoglobin concentration in the muscle, and finally the number of mitochondria in the muscle fibers [4]. Within the animal kingdom, horses have a high oxidative capacity, as indicated by maximal oxygen uptake of about 160 ml/kg body weight × min [15, 56], more than twice the uptake in human elite athletes. Theoretically, if it is assumed that during intense exercise 90% of oxygen is consumed by exercising muscles and that approximately 40% of the body weight is muscle, it can be calculated that with this oxygen uptake, aerobic ATP production in the equine muscle may approach 2 μmol × g-1 × s-1. This value is, however, well below the approximated maximal ATP demand, the calculated value of which for human muscle is about 3 μmol × g-1 × s-1([42]), and the difference indicated by these 2 figures has to be met by anaerobic glycolysis, an uneconomical but high-capacity pathway.

In human athletes, ATP production in glycolysis may be as high as 3 μmol/g body weight × s (Newsholme & Leech 1983), and although similar estimations from equine muscle are unavailable, the comparison of the activities of key glycolytic enzymes in equine muscles to those in human muscles [14, 25, 54, 8] indicates that anaerobic ATP production may be equally important in horses. Another product of glycolysis is NADH, which increases the cytosolic NADH/NAD+ ratio, which would rapidly slow down the rate of glycolysis. When the NADH/NAD+ ratio increases, glycolysis switches to the anaerobic mode. Instead of oxidation, pyruvate is reduced to lactate, and simultaneously NADH is oxidized to NAD+, which allows glycolysis to continue at the maximum rate. The need for NADH reoxidation in the cytoplasm means that the formation of lactic acid is essential for anaerobic energy production.

All muscle fibers contain the necessary enzyme lactate dehydrogenase. The activity of lactate dehydrogenase is, however, highest in those fibers that have the lowest volume density of mitochondria and the lowest number of capillaries per fiber area both in horses [31] as well as in other species [38, 20]. In horses these are usually the fast-twitch type IIB fibers [71]. In addition to this, lactate dehydrogenase activity in type IIB fibers is due almost exclusively to the muscle type isoenzyme that favors the reaction towards the formation of lactate, whereas in the slow-twitch fibers the isoenzyme that favors the oxidation of lactate to pyruvate is also present [38, 20]. Recently the activity of lactate dehydrogenase has been demonstrated also in mitochondria, which allows for an intracellular lactate shuttle and suggests that some of the lactate oxidation may occur in these organelles [6].

Effects of lactate on muscle metabolism

Accumulation of lactate in the muscle cells initiates a cascade that eventually leads to fatigue. In horses after intermittent maximal exercise lactate concentrations of the middle gluteal muscle may increase up to 200 mmol/kg dry weight, but in other maximal exercise tests values around 100 mmol/kg dry weight have been reported [64, 60, 72]. Also in exercising human subjects muscle lactate concentrations may reach 100 mmol/kg dry weight [59, 30]. Lactic acid increases the osmotic pressure of the muscle cell, which allows the extracellular water to move into the cell and increase the cell volume [32]. Interestingly, recent studies have suggested that cell volume is one of the major regulators of cell function. Increased volume may have a direct effect on energy metabolism, because swelling has an inhibitory effect on glycogen breakdown [33].

Because lactic acid is a relatively strong acid with a pKa-value of 3.86, at cellular pH it will be dissociated into a lactate anion and a proton, both of which have marked effects on metabolism [26]. Acidification of the cell will impair the function both of Ca2+-pumps and of Ca2+-channels on the sarcoplasmic reticulum and thus increase the relaxation time of the muscle sarcomeres [17, 26]. Protons also have a direct effect on the conformation of the myosin ATP-ase which is necessary for contraction [17, 26]. Furthermore, energy production will be slower, because protons inhibit the activity of the rate limiting enzyme of the glycolysis, phosphofructokinase, and also inhibit glycogen phosphorylation [17, 26]. In addition, the lactate anion has an inhibitory effect on the function of sarcomere. Because of all these events, muscles will work less efficiently, i.e., be fatigued (Fig. 2).
Figure 2

Effects of protons and the lactate anion on cell metabolism.

Several mechanisms in the muscle cell operate to prevent acidification and its consequences (Fig 3). The most important of these are buffer capacity and export of lactic acid from the muscle. The pH of the cell is maintained by buffer systems that include bicarbonate, protein, phosphate, and carnosine [58, 23]. The most efficient of these is the bicarbonate system, because it is an open system via the circulation and respiration. Protein content within the cell is high, and proteins function as buffers, as does the dipeptide carnosine. The concentration of the latter is especially high in equine muscles and is concentrated in the type IIB fibers [36, 12] which have the highest glycolytic and the lowest oxidative capacity [70]. Even though the buffer capacity of the trained equine muscle may be 50% higher than in human athletes [18, 40, 61], it is not high enough to prevent acidification. In horses after intense exercise muscle pH may drop to 6.5 to 6.4, while in human subjects the reported values range from 6.2 to 6.9 [34, 24, 29].
Figure 3

Regulation of pH in the muscle cell.

Transport of lactate from muscle

To delay acidification and thus to extend the time to exhaustion, lactate anions and protons can be exported from the muscle into interstitial space and blood plasma (Fig 4). Only the unprotonated form of lactic acid can freely diffuse through plasma membrane, because the phospholipid bilayer of the biological membranes prevents the passage of protons and lactate anions [29]. The role of nonionic diffusion increases with increasing lactic acid concentration and also when pH decreases. It can be calculated that at physiological pH, 7.4, 99.97% of lactic acid is dissociated, and at pH 6 the percentage is still 99.3. The role of nonionic diffusion is, however, greater than the proportion of undissociated lactic acid, because its high permeability through the membranes. From the muscle, protons formed during dissociation of lactic acid can be transported by the monocarboxylate transporter (MCT), or by the Na+/H+-exchange protein [29]. Comparison of the capacity of each of these systems – diffusion, Na+/H+ exchange and MCT – shows that MCT plays the major role; for instance, in human muscles the capacity of MCT to transport protons is markedly higher than the other two mechanisms combined [28].
Figure 4

Transport of lactate and protons across membranes.

Monocarboxylate transporters form a conserved protein family, the members of which are expressed in a species- and tissue-specific manner [21]. As indicated by their name, these proteins are not specific for lactate only, but transport other monocarboxylic acids, such as pyruvate, volatile fatty acids, and ketone bodies, as well. In all cases the transport is electroneutral; one monocarboxylate anion is transported together with a proton [49, 29]. The most extensively characterised MCT isoform is MCT1, which is expressed in most tissues. This isoform has been labeled by Halestrap and his group the "housekeeping" MCT [50]. Two isoforms of MCTs have been identified in the muscle tissue. Isoform 1 (MCT1) is the predominant isoform in the oxidative fibers, whereas in the fast-twitch, least oxidative, fibers, isoform 4 (MCT4) plays a major role [39, 73]. Several studies have shown that the expression of MCT1 is upregulated by training [39, 1, 3, 48, 11]. Interestingly, the activity and the amount of MCT1 appears to correlate with the percentage of oxidative fibers [1, 73], and it has been speculated that in oxidative fibers the role of MCT1 is to transfer lactate into the cells for oxidation, whereas MCT4 functions in the efflux of lactate from the muscle [1]. This notion is supported by the finding that the upregulation of MCT1 is accompanied by an increase in the activity of LDH1, the heart-type isoenzyme, indicating coexpression between the substrate transfer protein and the immediate enzyme the substrate faces in the cell [39, 11]. Since the MCT on the mitochondrial membranes is MCT1, the effect of training on the MCT1 expression may in part be due to the exercise-induced increase in the number of mitochondia [6]. MCT4 also increases with training [48, 11], but interindividual variation in this activation is large [11]. MCTs are activated at low pH [49]. Another important regulatory factor is the concentration gradient across the sarcolemma; as soon as lactate concentrations in the extracellular space approach that in the muscle, the efflux of lactate is attenuated.

In human subjects at exhaustion after dynamic knee extensor exercise, large interindividual differences in muscle pH occur [30, 35], which suggests that muscle sensitivity to low pH varies individually. It has also been shown that large interindividual differences exist in the post-exercise muscle-plasma lactate gradients [66]. Together, these results suggest that lactate transport across the sarcolemma provides a control site in lactate accumulation in the exercising muscle. It can be speculated that an individual with a high lactate transport capacity may produce more ATP from glycogen/glucose before the critical pH inside the cell is reached than an individual with a low lactate transport capacity. This is supported by two lines of evidence: First, some elite athletes have exceptionally high MCT activities, and second, human beings with a deficiency in MCT also suffer from exercise intolerance [16, 47]. More research will be needed to clarify the precise role of MCT in exercise performance and in the pH regulation of muscle.

Distribution of lactate in blood

The lactate anion as well as lactic acid is freely soluble in water and can thus be dispensed into the entire water space of the body, assuming that the necessary transport protein is available. From plasma, lactate is transported into red blood cells (RBC), liver, heart, all noncontractive muscles and other tissues (Fig 5). The direction of the lactate flow is determined mainly by the concentration gradient across the membranes of those tissues. The flow of lactate into the tissues will tend to decrease the plasma concentration of lactate and thus increase the efflux from the muscle which is determined by the muscle – plasma concentration gradient.

In the horse, RBC water space is especially interesting, because, during exercise, RBC account for about 60 per cent of the blood volume. RBC have active MCT on their plasma membranes, and they efficiently and rapidly take up lactate from plasma [69, 62]. Because the transporter has a rather high Km-value, about 20 mmol/l [62, 69], it thus cannot be saturated at physiological lactate concentrations. The activity of MCT in RBC is also activated by low pH [68]. It was recently suggested that high MCT activity in RBC membranes is a feature of athletic animal species such as dogs and horses [62]. In horses, RBC lactate is highly variable and has been connected with performance capacity, because among Standardbred trotters, those horses with the best individual performance index values have the highest lactate concentration in their RBC [51, 53]. The accumulation of lactate in RBC is also a function of MCT activity [68]. Our own studies of more than 100 Standardbred horses have demonstrated that in approximately 30% of the horses MCT activity in their RBC membranes is extremely low, and in these horses RBC lactate concentration is low after races [69, 68]. From our studies, it can be concluded that accumulation of lactate in RBC during exercise may have some impact on performance, but the issue is extremely complex, and the differences in the performance capacity between elite horses are small; thus, the causal relationship is extremely difficult to show conclusively. Interestingly, this high inherent interindividual variation seems to be a property of horses, because other athletic species that have been tested, human athletes, racing reindeer, sled dogs, and greyhounds, fail to show it [67].
Figure 5

Monocarboxylate transporters in lactate metabolism. Black squares mark monocarboxylate transporters, M = mitochondria.

Lactate accumulation in RBC during and after exercise has, however, a very large effect on the practice of lactate measurements, and on the question whether the post-exercise lactate concentration should be measured in whole blood or in plasma. On the basis of a large number of samples, there seems to be a good correlation between whole blood and plasma lactate concentrations [45, 51], but the situation differs completely if viewed on an individual basis. This can be demonstrated with "a real-life" example based on blood samples taken from two horses after a trotting race (Fig 6). One of these horses had high MCT activity in its RBC but in the other, this activity was low. In a blood samples taken from these two horses about 5 min after a race, the whole-blood lactate concentration was the same, 18.7–18.8 mmol/l, which may be taken as an indication that the amount of lactate transported from the muscle was the same. However, when part of the blood samples mentioned was immediately put on ice-water and plasma was rapidly separated by centrifugation and the plasma lactate concentrations were measured, the difference was striking: the horse having a low MCT activity had a high lactate concentration in plasma, whereas for the other horse more lactate had accumulated in the red blood cells and thus the plasma lactate concentration was low. This difference was not due to hematocrit values. This example demonstrates that if post-exercise lactate concentration is analysed in plasma samples, it is very difficult to make horse-to-horse comparisons. Interestingly, similar great individual muscle-blood lactate gradients exist in human athletes [66]. MCT activity is not the only factor influencing the accumulation of lactate in RBC in vitro [68]. The time from sampling to centrifugation and also the temperature at which the sample is stored have a great impact. If the blood sample is kept warm, the transport of lactate into RBC in the sample test tube is rapid, whereas if the samples are kept on ice no transport can be detected up to one hour. This may also be correlated with the ambient temperature, i.e., summer versus winter conditions. However, all these speculations on lactate distribution are unnecessary if whole blood lactate values are used.
Figure 6

Distribution of post-exercise lactate in blood samples of two horses. Samples for the measurement of whole blood lactate and plasma lactate were taken about 5 min after a 2100-m race. The sample for plasma lactate analysis was immediately cooled in ice-water and centrifuged at +4°C for separation of plasma.

Elimination of lactate during exercise and recovery

Transport of lactate into RBC is only a passive means to increase the muscle-plasma concentration gradient; the oxidation of lactate is more efficient. The latter occurs in the heart, liver, type I muscle fibers, and other noncontracting tissues both during exercise and especially after it [5]. The use of lactate differs between muscle tissue and liver. In the muscle, lactate is used for oxidation and energy production, and retains still over 90% of the energy of glucose. In liver, especially during exercise, lactate is metabolised back to glucose and circulated again to working muscles. During recovery, some lactate can be used for the synthesis of glycogen, although this matter is still under debate [65, 57]. This cell-to-cell lactate shuttle is well accepted, and recently a similar shuttle has been suggested to operate also within cell cytosol and mitochondria [7]. It is generally accepted that light exercise during recovery increases lactate disappearance from blood both in human subjects and in horses [37, 2, 19]. During recovery, muscle tissue, which on a percentage basis is the largest tissue of the body, changes from lactate producer to lactate consumer, because lactate is a good energy substrate and readily available. During light exercise, the oxygen consumption of muscle may be twice that at rest, an increase that is small in comparison to the 20-fold increase from rest to maximal aerobic exercise. This small increase in muscle oxygen consumption will also double the utilisation of lactate in muscle, seen as faster disappearance [22].

Lactate as a marker of performance

Several factors affect blood lactate concentration (Fig. 7), and at least some of these factors are influenced by training. The rate of lactate production in exercising muscles is influenced by oxidative capacity, and thus training which is often accompanied with an increase in the number of mitochondria may reduce lactate production. Another factor that may regulate blood lactate concentration is the rate of efflux from the muscle, and as mentioned earlier, training increases the number of monocarboxylate transport proteins on the sarcolemma, which would have the effect of increasing blood lactate concentration. The third factor that markedly influences blood lactate concentration is its uptake by tissues that oxidize lactate. Several studies in humans have shown that lactate is taken up by the liver and inactive muscles and that lactate clearance is increased by training [10, 43, 46]. Increased clearance during and after exercise would tend to lower the lactate concentration in blood. All these factors have to be taken into account when blood lactate concentration serves as a marker of performance.

What does blood lactate concentration tell us about performance? Primarily, it is a useful marker for the estimation of aerobic capacity. It is well known that the trained horses have high aerobic capacity and at a certain absolute work intensity produce less lactate than do horses that are not equally well trained [63, 44]. In races, horses perform at maximal intensity and use their anaerobic capacity, as well. For this anaerobic capacity, lactate is not an equally good marker, because we still have insufficient basic knowledge of those systems contributing to blood lactate concentration. For two horses working at maximal intensity, one with a high lactate and the other a substantially lower maximal lactate concentration, there are still several factors that remain question marks in this equation. Did one horse have a low concentration of lactate because it did not have high activity of MCT on its sarcolemmal membranes, or did it have less lactate production in its muscles because of higher aerobic capacity or because of lower activity of its glycolytic enzymes? Was the fiber recruitement pattern the same in the two horses? Or was the buffer capacity different in the muscles; did one horse tolerate lower lactate concentrations in its muscles? What if the uptake of lactate into liver and other user tissues differed between these two horses? From a practical point of view, knowledge of aerobic capacity is valuable, because high capacity would mean that lactate concentration for a major part of the race will be lower than that of a horse with low oxidative capacity. We should not, however, forget that what is important is not the blood lactate, but the lactate concentration in the muscle and perhaps also the activity of MCT in muscle membranes.
Figure 7

Factors affecting plasma lactate concentration.

Figure 1

Oxidation of carbohydrates in glycolysis.

Notes

Authors’ Affiliations

(1)
Department of Basic Veterinary Sciences, University of Helsinki

References

  1. Baker SK, McCullagh KJA, Bonen A: Training intensity-dependent and tissue-specific increases in lactate uptake and MCT-1 in heart and muscle. J appl Physiol. 1998, 84: 987-994. 10.1063/1.368165.View ArticlePubMedGoogle Scholar
  2. Bangsbo J, Graham T, Johansen L, Saltin B: Muscle lactate metabolism in recovery from intense echaustive exercise: Impact of light exercise. J appl Physiol. 1994, 77: 1980-1985.Google Scholar
  3. Bonen A, McCullagh KJA, Putman CT, Hultman E, Jones NL, Heigenhauser GJF: Short-term training increases human muscle MCT1 and femoral venous lactate in relation to muscle lactate. Am J Physiol. 1998, 274: E102-E107.PubMedGoogle Scholar
  4. Booth FW, Thomason DB: Molecular and cellular adaptation of muscle in response to exercise: Perspectives of various models. Physiol Rev. 1991, 71: 541-585.PubMedGoogle Scholar
  5. Brooks GA: Current concepts in lactate exchange. Med Sci Sports Exerc. 1991, 23: 895-906.View ArticlePubMedGoogle Scholar
  6. Brooks GA, Brown MA, Butz CE, Sicurello JP, Dubouchaud H: Cardiac and skeletal muscle mitochondria have a monocarboxylate transporter MCT1. J appl Physiol. 1999, 87: 1713-1718.PubMedGoogle Scholar
  7. Brooks GA, Dubouchaud H, Brown M, Sicurello JP, Butz CE: Role of mitochondrial lactate dehydrogenase and lactate oxidation in the intracellular lactate shuttle. Proc natl Acad Sci USA. 1999, 96: 1129-1134. 10.1073/pnas.96.3.1129.PubMed CentralView ArticlePubMedGoogle Scholar
  8. Cutmore CMM, Snow DH, Newsholme EA: Activities of key enzymes of aerobic and anaerobic metabolism in middle gluteal muscle from trained and untrained horses. Equine vet J. 1993, 17: 354-356.View ArticleGoogle Scholar
  9. Derman KD, Noakes TD: Comparative aspects of exercise physiology. The Athletic Horse. Edited by: Hodgson DR, Rose RJ. 1994, Philadelphia, PA, Saunders, 13-25.Google Scholar
  10. Donovan CM, Brooks GA: Endurance training affects lactate clearance not lactate production. Am J Physiol. 1983, 244: E83-E92.PubMedGoogle Scholar
  11. Dubouchaud H, Butterfied GE, Wolfel EE, Bergman BC, Brooks GA: Endurance training, expression, and physiology of LDH, MCT1, and MCT4 in human skeletal muscle. Am J Physiol. 2000, 278: E571-E579.Google Scholar
  12. Dunnett M, Harris RC: Carnosine and taurine contents of type I, IIA and IIB fibers in the middle gluteal muscle. Equine vet J. 1995, 214-217. Suppl 18
  13. Eaton MD: Energetics and performance. The Athletic Horse. Edited by: Hodgins DR, Rose RJ. 1994, Philadelphia, PA, Saunders, 49-61.Google Scholar
  14. Essén-Gustavsson B, Karlström K, Lindholm A: Fibre types, enzyme activities and substrate utilisation in skeletal muscles of horses competing in endurance races. Equine vet J. 1984, 16: 197-202.View ArticlePubMedGoogle Scholar
  15. Evans DL, Rose RJ: Determination and repeatability of maximum oxygen uptake and other cardiorespiratory measurements in the exercising horse. Equine vet J. 1988, 20: 94-98.View ArticlePubMedGoogle Scholar
  16. Fishbein WN: Lactate transporter defect: a new disease of muscle. Science. 1986, 234: 1254-1256. 10.1126/science.3775384.View ArticlePubMedGoogle Scholar
  17. Fitts RH: Cellular mechanisms of muscle fatigue. Physiol Rev. 1994, 4: 49-94.Google Scholar
  18. Fox G, Henckel P, Juel C, Falk-Rønne J, Saltin B: Skeletal muscle buffer capacity changes in Standardbred horses: effects of growth and training. Equine Exercise Physiology 2. Edited by: Gillespie JR, Robinson NE. 1987, Davis, CA, ICEEP Publications, 341-347.Google Scholar
  19. Francaux M, Jacqmin J, Dewelle JM, Sturbois X: A study of lactate metabolism without tracer during passive and active postexercise recovery in humans. Eur J appl Physiol. 1995, 72: 58-66. 10.1007/BF00964115.View ArticleGoogle Scholar
  20. Grichko VP, Gettelman GJ, Widrick JJ, Fitts RH: Substrate and enzyme profile of fast and slow skeletal muscle fibers in rhesus monkeys. J appl Physiol. 1999, 86: 335-340.PubMedGoogle Scholar
  21. Halestrap AP, Price NT: The proton-linked monocarboxylate transporter (MCT) family: structure, function and regulation. Biochem J. 1999, 343: 281-299. 10.1042/0264-6021:3430281.PubMed CentralView ArticlePubMedGoogle Scholar
  22. Halperin ML, Rolleston FS: Clinical Detective Stories. 1993, London, Portland Press, 258-Google Scholar
  23. Harris RC, Marlin DJ, Dunnett M, Snow DH, Hultman E: Muscle buffering capacity and dipeptide content in teh Thoroughbred horse, Greyhound dog and man. Comp Biochem Physiol. 1990, 97: 249-251. 10.1016/0300-9629(90)90180-Z.View ArticleGoogle Scholar
  24. Harris RC, Snow DH, Katz A, Sahlin K: Effect of freeze-drying on measurements of pH in biopsy samples of the middle gluteal muscle of the horse: comparison of muscle pH to the pyruvate and lactate content. Equine vet J. 1989, 21: 45-47.View ArticlePubMedGoogle Scholar
  25. Henriksson J, Chi MMY, Hintz CS, Young DA, Kaiser KK, Salmons S, Lowry OH: Chronic stimulation of mammalian muscle: changes in enzyme of six metabolic pathways. Am J Physiol. 1986, 251: C614-C632.PubMedGoogle Scholar
  26. Hyyppä S, Pösö AR: Fluid, electrolyte, and acid-base responses to exercise in racehorses. Vet Clin NA: Equine Pract. 1998, 14: 121-136.Google Scholar
  27. Jones WE: Equine Sports Medicine. 1989, Philadelphia, PA, Lea & Febiger, 121-136.Google Scholar
  28. Juel C: Lactate/proton co-transport in skeletal muscle: regulation and importance for pH homeostasis. Acta physiol scand. 1996, 156: 369-374. 10.1046/j.1365-201X.1996.206000.x.View ArticlePubMedGoogle Scholar
  29. Juel C: Lactate-proton cotransport in skeletal muscle. Physiol Rev. 1997, 77: 321-358.PubMedGoogle Scholar
  30. Juel C, Bangsbo J, Graham T, Saltin B: Lactate and potassium fluxes from human skeletal muscle during and after intense, dynamic, knee extensor exercise. Acta physiol scand. 1990, 140: 147-159.View ArticlePubMedGoogle Scholar
  31. Karlström K, Essén-Gustavsson B, Lindholm A: Fibre type distribution, capillarization and enzymatic profile of locomotor and nonlocomotor muscles of horses and steers. Acta anat. 1994, 151: 97-106.View ArticlePubMedGoogle Scholar
  32. Kingston JK, Bayly WM: Effect of exercise on acidbase status of horses. Vet Clin NA: Equine Pract. 1998, 14: 61-73.Google Scholar
  33. Lang F, Busch GL, Ritter M, Volkl H, Waldegger S, Gulbins E, Haussinger D: Functional significance of cell volume regulatory mechanisms. Physiol Rev. 1998, 78: 247-306.PubMedGoogle Scholar
  34. Lovell DK, Reid TA, Rose RJ: Effects of maximal exercise on equine muscle: changes in metabolites, pH and temperature. Equine Exercise Physiology 2. Edited by: Gillespie JR, Robinson NE. 1987, Davis, CA, ICEEP Publications, 312-320.Google Scholar
  35. Mannion AF, Jakeman PM, Willan PLT: Skeletal muscle buffer value, fibre type distribution and high intensity exercise performance in man. Exp Physiol. 1995, 80: 89-101.View ArticlePubMedGoogle Scholar
  36. Marlin DJ, Harris RC: Carnosine content of the middle gluteal muscle in Thoroughbred horses with relation to age, sex and training. Comp Biochem Physiol. 1989, 93: 629-632. 10.1016/0300-9629(89)90023-6.View ArticleGoogle Scholar
  37. Marlin DJ, Harris RC, Harman JC, Snow DH: Influence of post-exercise activity on rates of muscle and blood lactate disappearance in the Thoroughbred horse. Equine Exercise Physiology 2. Edited by: Gillespie JR, Robinson NE. 1987, Davis CA. ICEEP Publications, 321-331.Google Scholar
  38. McCullagh KJA, Poole RC, Halestrap AP, O'Brien M, Bonen A: Role of lactate transporter (MCT) in skeletal muscles. Am J Physiol. 1996, 271: E143-E150.PubMedGoogle Scholar
  39. McCullagh KJA, Poole RC, Halestrap AP, Tipton KF, O'Brien M, Bonen A: Chronic electrical stimulation increases MCT1 and lactate uptake in red and white skeletal muscle. Am J Physiol. 1997, 273: E239-E246.PubMedGoogle Scholar
  40. McCutcheon LJ, Kelso TB, Bertocci LA, Hodgson DR, Bayly WM, Gollnick PD: Buffering and aerobic capacity in equine muscle: variation and effect of training. Equine Exercise Physiology 2. Edited by: Gillespie JR, Robinson NE. 1987, Davis, CA, ICEEP Publications, 348-358.Google Scholar
  41. McMiken D: Muscle fiber types and horse performance. Equine Pract. 1986, 8: 6-15.Google Scholar
  42. Newsholme EA, Leech AR: Biochemistry for the Medical Sciences. 1986, Chichester, John Wiley & Sons, 357-381.Google Scholar
  43. Pagliassotti MJ, Donovan CM: Role of cell type in net lactate removal by skeletal muscle. Am J Physiol. 1990, 258: E635-E642.PubMedGoogle Scholar
  44. Persson SGB: Evaluation of exercise tolerance and fitness in the performance horse. Equine Exercise Physiology. Edited by: Snow DH, Persson SGB, Rose RJ. 1983, Cambridge, Granta Editions, 441-457.Google Scholar
  45. Persson SGB, Essén-Gustavsson B, Funkquist P, Romero LB: Plasma, red cell and whole blood lactate concentrations during prolonged treadmill exercise at VLA4. Equine vet J. 1995, 104-107. Suppl 18
  46. Phillips SM, Green HJ, Tarnopolsky MA, Grant SM: Increased clearance of lactate after short-term training in men. J appl Physiol. 1995, 79: 1862-1869.PubMedGoogle Scholar
  47. Pilegaard H, Bangsbo J, Richter EA, Juel C: Lactate transport studied in sarcolemmal giant vesicles from human muscle biopsies: relation to training status. J appl Physiol. 1994, 77: 1858-1862.PubMedGoogle Scholar
  48. Pilegaard H, Domino K, Noland T, Juel C, Hellsten Y, Halestrap AP, Bangsbo J: Effect of high-intensity exercise training on lactate/H+ transport capacity in human skeletal muscle. Am J Physiol. 1999, 276: E255-E261.PubMedGoogle Scholar
  49. Poole RC, Halestrap AP: Transport of lactate and other monocarboxylates across mammalian plasma membranes. Am J Physiol. 1993, 264: C761-C782.PubMedGoogle Scholar
  50. Poole RC, Sansom CE, Halestrap AP: Studies of the membrane topology of the rat erythcoryte H+ /Lactate cotransporter (MCT1). Biochem J. 1996, 320: 817-824.PubMed CentralView ArticlePubMedGoogle Scholar
  51. Pösö AR, Lampinen KJ, Räsänen LA: Distribution of lactate between red blood cells and plasma after exercise. Equine vet J. 1995, 231-234. Suppl 18
  52. Pösö AR, Nieminen M, Raulio J, Räsänen LA, Soveri T: Skeletal muscle characteristics of racing reindeer (Rangifer tarandus). Comp Biochem Physiol. 1996, 114A: 277-281. 10.1016/0300-9629(96)00014-X.View ArticleGoogle Scholar
  53. Räsänen LA, Lampinen KJ, Pösö AR: Responses of blood and plasma lactate and plasma purine concentrations to maximal exercise and their relation to performance in Standardbred trotters. Am J vet Res. 1995, 56: 1651-1656.PubMedGoogle Scholar
  54. Ronéus M, Lindholm A, Åsheim Å: Muscle characteristics of Thoroughbreds of different ages and sexes. Equine vet J. 1991, 23: 207-210.View ArticlePubMedGoogle Scholar
  55. Ronéus M, Persson SGB, Essén-Gustavsson B, Árnason T: Skeletal muscle characteristics in red blood cell normovolaemic and hypervolaemic Standardbred racehorse. Equine vet J. 1994, 26: 319-322.View ArticlePubMedGoogle Scholar
  56. Rose RJ, Hodgson DR, Kelso TB, McCutcheon LJ, Reid TA, Bayly WM, Gollnick PD: Maximum O2 uptake, O2 debt and deficit, and muscle metabolites in Thoroughbred horses. J appl Physiol. 1988, 64: 781-788.PubMedGoogle Scholar
  57. Ryan C, Radziuk J: Distinguishable substrate pools for muscle glyconeogenesis in lactate-supplemented recovery from exercise. Am J Physiol. 1995, 269: E538-E550.PubMedGoogle Scholar
  58. Sahlin K, Henriksson J: Buffer capacity and lactate accumulation in skeletal muscle of trained and untrained men. Acta physiol scand. 1984, 122: 331-339.View ArticlePubMedGoogle Scholar
  59. Sahlin K, Broberg S, Ren JM: Formation of inosine monophosphate (IMP) in human skeletal muscle during incremental dynamic exercise. Acta physiol. scand. 1989, 136: 193-198.Google Scholar
  60. Schuback K, Essén-Gustavsson B: Muscle anaerobic response to a maximal treadmill exercise test in Standardbred trotters. Equine vet J. 1998, 30: 504-510.View ArticlePubMedGoogle Scholar
  61. Sewell DA, Harris RC, Dunnett M: Carnosine accounts for most of the variation in physico-chemical buffering in equine muscle. Equine Exercise Physiology 3. Edited by: Persson SGB, Lindholm A, Jeffcott LB. 1991, Davis, CA, ICEEP Publications, 276-280.Google Scholar
  62. Skelton MS, Kremer DE, Smith EW, Gladden LB: Lactate influx into red blood cells of athletic and nonathletic species. Am J Physiol. 1995, 268: R1121-R1128.PubMedGoogle Scholar
  63. Snow DH, MacKenzie G: Some metabolic effects of maximal exercise in the horse and adaptations with training. Equine vet J. 1977, 9: 134-140.View ArticlePubMedGoogle Scholar
  64. Snow DH, Harris RC, Gash SP: Metabolic response of equine muscle to intermittent maximal exercise. J appl Physiol. 1985, 58: 1689-1697. 10.1063/1.336065.View ArticlePubMedGoogle Scholar
  65. Stevenson RW, Mitchell DR, Hendrick GK, Rainey R, Cherrington AD, Frizzell RD: Lactate as substrate for glycogen resynthesis after exercise. J appl Physiol. 1987, 62: 2237-2240. 10.1063/1.339499.View ArticlePubMedGoogle Scholar
  66. Tesch PA, Daniels WL, Sharp DS: Lactate accumulation in muscle and blood during submaximal exercise. Acta physiol scand. 1982, 114: 441-446.View ArticlePubMedGoogle Scholar
  67. Väihkönen LK, Heinonen OJ, Hyyppä S, Nieminen M, Pösö AR: Lactate transport activity in red blood cells of trained and untrained individuals from four racing species. Am J Physiol. 2001, 281: R19-R24.Google Scholar
  68. Väihkönen LK, Hyyppä S, Pösö AR: Factors affecting accumulation of lactate in red blood cells. Equine vet J. 1999, 443-447. Suppl 30
  69. Väihkönen LK, Pösö AR: Interindividual variation in total and carrier mediated lactate influx into red blood cells. Am J Physiol. 1998, 274: R1121-R1128.Google Scholar
  70. Valberg S: Metabolic response to racing and fibre properties of skeletal muscle in standardbred and thoroughbred horses. J equine vet Sci. 1987, 7: 6-12. 10.1016/S0737-0806(87)80085-0.View ArticleGoogle Scholar
  71. Valberg S, Essén-Gustavsson B: Metabolic response to racing determined in pools of type I, IIA and IIB fibers. Equine Exercise Physiology 2. Edited by: Gillespie JR, Robinson NE. 1987, Davis, CA, ICEEP Publications, 290-301.Google Scholar
  72. Valberg SJ, Macleay JM, Billstrom JA, Hower-Moritz MA, Mickelson JR: Skeletal muscle metabolic response to exercise in horses with 'tying-up' due to polysaccharide storage myopathy. Equine vet J. 1999, 31: 43-47.View ArticlePubMedGoogle Scholar
  73. Wilson MC, Jackson VN, Heddle C, Price NT, Pilegaard H, Juel C, Bonen A, Montgomery I, Hutter OF, Halestrap AP: Lactic acid efflux from white skeletal muscle is catalyzed by the monocarboxylate transporter isoform MCT3 (MCT4). J biol Chem. 1998, 273: 15920-15926. 10.1074/jbc.273.26.15920.View ArticlePubMedGoogle Scholar

Copyright

© The Author(s) 2002