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Training-induced changes in membrane transport proteins of human skeletal muscle

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Abstract

Training improves human physical performance by inducing structural and cardiovascular changes, metabolic changes, and changes in the density of membrane transport proteins. This review focuses on the training-induced changes in proteins involved in sarcolemmal membrane transport. It is concluded that the same type of training affects many transport proteins, suggesting that all transport proteins increase with training, and that both sprint and endurance training in humans increase the density of most membrane transport proteins. There seems to be an upper limit for these changes: intense training for 6–8 weeks substantially increases the density of membrane proteins, whereas years of training (as performed by athletes) have no further effect. Studies suggest that training-induced changes at the protein level are important functionally. The underlying factors responsible for these changes in transport proteins might include changes in substrate concentration, but the existence of “exercise factors” mediating these responses is more likely. Exercise factors might include Ca2+, mitogen-activated protein kinases, adenosine monophosphate kinases, other kinases, or interleukin-6. Although the magnitudes of training-induced changes have been investigated at the protein level, the underlying signal mechanisms have not been fully described.

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References

  • Bergman BC, Wolfel EE, Butterfield GE, Lopaschuk GD, Casazza GA, Horning MA, Brooks GA (1999) Active muscle and whole body lactate kinetics after endurance training in men. J Appl Physiol 87:1684–1696

    PubMed  CAS  Google Scholar 

  • Biolo G, Williams BD, Fleming RY, Wolfe RR (1999) Insulin action on muscle protein kinetics and amino acid transport during recovery after resistance exercise. Diabetes 48:949–957

    Article  PubMed  CAS  Google Scholar 

  • Bonen A, McCullagh KJ, Putman CT, Hultman E, Jones NL, Heigenhauser GJ (1998) Short-term training increases human muscle MCT1 and femoral venous lactate in relation to muscle lactate. Am J Physiol 274:E102–E107

    PubMed  CAS  Google Scholar 

  • Brooks GA, Brown MA, Butz CE, Sicurello JP, Dubouchaud H (1999) Cardiac and skeletal muscle mitochondria have a monocarboxylate transporter MCT1. J Appl Physiol 87:1713–1718

    PubMed  CAS  Google Scholar 

  • Christ-Roberts CY, Pratipanawatr W, Berria R, Belfort R, Kashyap S, Mandarino LJ (2004) Exercise training increases glycogen synthase activity and GLUT4 expression but not insulin signalling in overweight nondiabetic and type 2 diabetic subjects. Metabolism 53:1233–1242

    Article  PubMed  CAS  Google Scholar 

  • Clausen T (2003) Na+,K+ pump regulation and skeletal muscle contractility. Physiol Rev 83:665–673

    Google Scholar 

  • Coles L, Litt J, Hatta H, Bonen A (2004) Exercise rapidly increases expression of the monocarboxylate transporters MCT1 and MCT4 in rat muscle. J Physiol 561:253–261

    Article  PubMed  CAS  Google Scholar 

  • Dela F, Ploug T, Handberg A, Petersen LN, Larsen JJ, Mikines KL, Galbo H (1994) Physical training increases muscle GLUT4 protein and mRNA in patients with NIDDM. Diabetes 43:862–865

    Article  PubMed  CAS  Google Scholar 

  • Dela F, Holten M, Juel C (2004) Effect of resistance training on Na,K-pump and Na+/H+ exchange protein densities in muscle from control and patients with type 2 diabetes. Pflügers Arch Eur J Physiol 447:928–933

    Article  CAS  Google Scholar 

  • Derave W, Eijnde BO, Verbessem P, Ramaekers M, Van Leemputte M, Richter EA, Hespel P (2003) Combined creatine and protein supplementation in conjunction with resistance training promotes muscle GLUT-4 content and glucose tolerance in humans. J Appl Physiol 94:1910–1916

    PubMed  CAS  Google Scholar 

  • Dubouchaud H, Butterfield GE, Wolfel EE, Bergman BC, Brooks GA (2000) Endurance training, expression, and physiology of LDH, MCT1, and MCT4 in human skeletal muscle. Am J Physiol 278:E571–E578

    PubMed  CAS  Google Scholar 

  • Evertsen F, Medbø JI, Jebens E, Nicolaisen K (1997) Hard training for 5 month increases Na+-K+-pump concentration in skeletal muscle of cross-country skiers. Am J Physiol 272:R1417–R1424

    PubMed  CAS  Google Scholar 

  • Fischer H, Gustafsson T, Sundberg CJ, Jansson E (2005) Fatty acid binding protein 4 is detected in human skeletal muscle and nodulated by endurance exercise. In: Experimental biology meeting 2005, abstract LB137

  • Fraser SF, Li JL, Carey MF, Wang XN, Sangkabutra T, Sostaric S, Selig SE, Kjeldsen K, McKenna MJ (2002) Fatigue depresses maximal in vitro skeletal muscle Na(+)-K(+)-ATPase activity in untrained and trained individuals. J Appl Physiol 93:1650–1659

    PubMed  CAS  Google Scholar 

  • Friedlander AL, Casazza GA, Horning MA, Huie MJ, Brooks GA (1997) Training-induced alterations of glucose flux in men. J Appl Physiol 82:1360–1369

    PubMed  CAS  Google Scholar 

  • Friedlander AL, Casazza GA, Horning MA, Buddinger TF, Brooks GA (1998) Effects of exercise intensity and training on lipid metabolism in young women. Am J Physiol 275:E853–E863

    PubMed  CAS  Google Scholar 

  • Frigeri A, Nicchia GP, Desaphy J-F, Pierno S, Luca A, Camerino DC, Svelto M (2001) Muscle loading modulates aquaporin-4 expression in skeletal muscle. FASEB J 15:1282–1284

    Article  PubMed  CAS  Google Scholar 

  • Frigeri A, Nicchia GP, Balena R, Nico B, Svelto M (2004) Aquaporins in skeletal muscle: reassessment of the functional role of aquaporin-4. FASEB J 18:905–907

    PubMed  CAS  Google Scholar 

  • Garcia CK, Goldstein JL, Pathak RK, Anderson GW, Brown MS (1994) Molecular characterization of a membrane transporter for lactate, pyruvate, and other monocarboxylates: implications for the Cory cycle. Cell 76:865–873

    Article  PubMed  CAS  Google Scholar 

  • Gaster M, Handberg A, Schurmann A, Joost HG, Beck-Nielsen H, Schroder HD (2004) GLUT11, but not GLUT8 or GLUT12, is expressed in human skeletal muscle in a fiber type-specific pattern. Pflugers Arch 448:105–113

    Article  PubMed  CAS  Google Scholar 

  • Gosmanow AR, Nordtvedt NC, Brown R, Thomason DB (2002) Exercise effects on muscle β-adrenergic signaling for MAPK-dependent NKCC activity are rapid and persistent. J Appl Physiol 93:1457–1465

    PubMed  Google Scholar 

  • Green HJ, Chin ER, Ball-Burnett M, Ranney D (1993) Increases in human skeletal muscle Na(+)-K(+)-ATPase concentration with short-term training. Am J Physiol 264:C1538–C1541

    PubMed  CAS  Google Scholar 

  • Green H, Dahly A, Shoemaker K, Goreham C, Bombardier E, Ball-Burnett M (1999) Serial effects of high-resistance and prolonged endurance training on Na+–K+ pump concentration and enzymatic activities in human vastus lateralis. Acta Physiol Scand 165:177–184

    Article  PubMed  CAS  Google Scholar 

  • Grunze M, Forst B, Deuticke B (1980) Dual effect of membrane cholesterol on simple and mediated transport processes in human erythrocytes. Biochim Biophys Acta 600:860–869

    Article  PubMed  CAS  Google Scholar 

  • Halestrap AP, Meredith D (2004) The SLC16 gene family—from monocarboxylate transporters (MCTs) to aromatic amino acid transporters and beyond. Pflügers Arch Eur J Physiol 447:619–628

    Article  CAS  Google Scholar 

  • Hayashi T, Hirshman MF, Fujii N, Habinowski SA, Witters LA, Goodyear LJ (2000) Metabolic stress and altered glucose transport activation of AMP-activated protein kinase as a unifying coupling mechanism. Diabetes 49:1–4

    Article  PubMed  Google Scholar 

  • Helge JW, Wu BJ, Willer M, Daugaard JR, Storlien LH, Kiens B (2001) Training affects muscle phospholipid fatty acid composition in humans. J Appl Physiol 90:670–677

    Article  PubMed  CAS  Google Scholar 

  • Holten MK, Zacho M, Juel C, Wojtascewski J, Dela F (2004) Strength training increases insulin mediated glucose uptake, GLUT-4 content and insulin signaling in skeletal muscle in patients with type 2 diabetes. Diabetes 53:294–305

    Article  PubMed  CAS  Google Scholar 

  • Hundal HS, Darakhahan F, Kristiansen S, Blakemore SJ, Richter EA (1998) GLUT5 expression and fructose transport in human skeletal muscle. Adv Exp Med Biol 441:35–45

    PubMed  CAS  Google Scholar 

  • Hyde R, Peyrollier K, Hundal HS (2002) Insulin promotes the cell surface recruitment of the SAT2/ATA2 system A amino acid transporter from an endosomal compartment in skeletal muscle cells. J Biol Chem 277:13628–13634

    Article  PubMed  CAS  Google Scholar 

  • Juel C (1991) Muscle lactate transport studied in sarcolemmal giant vesicles. Biochim Biophys Acta 1065:15–20

    Article  PubMed  CAS  Google Scholar 

  • Juel C (1995) Regulation of cellular pH in skeletal muscle fiber types, studied with sarcolemmal giant vesicles obtained from rat muscles. Biochim Biophys Acta 1265:127–132

    Article  PubMed  Google Scholar 

  • Juel C (1996) Lactate/proton co-transport in skeletal muscle: regulation and importance for pH homeostasis. Acta Physiol Scand 156:369–474

    Article  PubMed  CAS  Google Scholar 

  • Juel C (1997) Lactate–proton cotransport in skeletal muscle. Physiol Rev 77:321–358

    PubMed  CAS  Google Scholar 

  • Juel C (1998a) Muscle pH regulation: role of training. Acta Physiol Scand 162:359–366

    Article  CAS  Google Scholar 

  • Juel C (1998b) Skeletal muscle Na+/H+ exchange in rats: pH dependency and the effect of training. Acta Physiol Scand 164:135–140

    Article  CAS  Google Scholar 

  • Juel C (2000) Expression of the Na+/H+ exchanger isoform NHE1 in rat skeletal muscle and effect of training. Acta Physiol Scand 170:59–63

    Article  PubMed  CAS  Google Scholar 

  • Juel C, Halestrap AP (1999) Lactate transport in skeletal muscle—role and regulation of the monocarboxylate transporter. J Physiol 517:633–642

    Article  PubMed  CAS  Google Scholar 

  • Juel C, Kristiansen S, Pilegaard H, Wojtaszewski J, Richter EA (1994) Kinetics of lactate transport in sarcolemmal giant vesicles obtained from human skeletal muscle. J Appl Physiol 76:1031–1036

    PubMed  CAS  Google Scholar 

  • Juel C, Nielsen JJ, Bangsbo J (2000) Exercise-induced translocation of Na+–K+ pump subunits to the plasma membrane in human skeletal muscle. Am J Physiol 278:R1107–R1110

    CAS  Google Scholar 

  • Juel C, Grunnet L, Holse M, Kenworthy S, Sommer V, Wulff T (2001) Reversibility of exercise-induced translocation of Na+–K+ pump subunits to the plasma membrane in rat skeletal muscle. Pflügers Arch Eur J Physiol 443:212–217

    Article  CAS  Google Scholar 

  • Juel C, Lundbye C, Sander M, Calber JAL, van Hall G (2003) Human skeletal muscle and erythrocyte proteins involved in acid–base homeostasis: adaptations to chronic hypoxia. J Physiol 548:639–648

    Article  PubMed  CAS  Google Scholar 

  • Juel C, Holten MK, Dela F (2004a) Effect of strength training on muscle lactate release and MCT1 and MCT4 content in healthy and type 2 diabetic humans. J Physiol 556:297–304

    Article  CAS  Google Scholar 

  • Juel C, Klarskov C, Nielsen JJ, Krustrup P, Mohr, Bangsbo J (2004b) Effect of high-intensity intermittent training on lactate and H+ release from human skeletal muscle. Am J Physiol Endocrinol Metab 286:E245–E251

    Article  CAS  Google Scholar 

  • Kiens B, Kristiansen S, Jensen P, Richter EA, Turcotte LP (1997) Membrane associated fatty acid binding protein (FABPpm) in human skeletal muscle is increased by endurance training. Biochem Biophys Res Commun 231:463–465

    Article  PubMed  CAS  Google Scholar 

  • Kim HJ, Lee JS, Kim CK (2004) Effect of exercise training on muscle glucose transporters 4 protein and intramuscular lipid content in elderly men with impaired glucose tolerance. Eur J Appl Physiol 93:353–358

    Article  PubMed  CAS  Google Scholar 

  • Klitgaard H, Clausen T (1989) Increased total concentration of Na–K pumps in vastus lateralis muscle of old trained human subjects. J Appl Physiol 67:2491–2494

    PubMed  CAS  Google Scholar 

  • Kraniou G, Cameron-Smith D, Hargreaves M (2004) Effect of short-term training on GLUT-4 mRNA and protein expression in human skeletal muscle. Exp Physiol 89:559–563

    Article  PubMed  CAS  Google Scholar 

  • Kristensen JM, Kristensen M, Juel C (2004) Expression of Na+/HCO −3 co-transporter proteins (NBCs) in rat and human skeletal muscle. Acta Physiol Scand 182:69–76

    Article  PubMed  CAS  Google Scholar 

  • Kristensen M, Hansen T, Juel C (2006) Membrane proteins involved in the potassium shifts during muscle activity and fatigue. Am J Physiol (in press)

  • Kristiansen S, Gade J, Wojtaszewski JF, Kiens B, Richter EA (2000) Glucose uptake is increased in trained vs. untrained muscle during heavy exercise. J Appl Physiol 89:1151–1158

    PubMed  CAS  Google Scholar 

  • Kurth-Kraczek EJ, Hirshman MF, Goodyear LJ, Winder WW (1999) 5′AMP-activated protein kinase activation causes GLUT4 translocation in skeletal muscle. Diabetes 48:1667–1671

    Article  PubMed  CAS  Google Scholar 

  • Langfort J, Viese M, Ploug T, Dela F (2003) Time course of GLUT4 and AMPK protein expression in human skeletal muscle during one month of physical training. Scand J Med Sports 13:169–174

    Article  CAS  Google Scholar 

  • Lynge J, Juel C, Hellsten Y (2001) Extracellular formation and uptake of adenosine during skeletal muscle contraction: role of adenosine transporters. J Physiol 537:597–605

    Article  PubMed  CAS  Google Scholar 

  • Madsen K, Franch J, Clausen T (1994) Effects of intensified endurance training on the concentration of Na,K-ATPase and Ca-ATPase in human skeletal muscle. Acta Physiol Scand 150:251–258

    PubMed  CAS  Google Scholar 

  • McConell GK, Lee-Young RS, Chen Z, Stepto NK, Huynh NN, Stephens TJ, Canny BJ, Kemp BE (2005) Short-term exercise training in humans reduces AMPK signalling during prolonged exercise independent of muscle glycogen. J Physiol 568:665–676

    Article  PubMed  CAS  Google Scholar 

  • McCullagh KJA, Juel C, O’Brian M, Bonen A (1996) Chronic muscle stimulation increases lactate transport in rat skeletal muscle. Mol Cell Biochem 156:51–57

    Article  PubMed  CAS  Google Scholar 

  • McKenna MJ, Schmidt TA, Hargreaves M, Cameron L, Skinner SL, Kjeldsen K (1993) Sprint training increases human skeletal muscle Na+-K+-ATPase concentration and improves K+ regulation. J Appl Physiol 75:173–180

    PubMed  CAS  Google Scholar 

  • Murphy KT, Snow RJ, Petersen AC, Murphy RM, Mollica J, Lee JS, Garnham AP, Aughey RJ, Leppik JA, Medved I, Cameron-Smith D, McKenna MJ (2004) Intense exercise up-regulates Na+,K+-ATPase isoform mRNA, but not protein expression in human skeletal muscle. J Physiol 556:507–519

    Article  PubMed  CAS  Google Scholar 

  • Musi N, Yu K, Goodyear LJ (2003) AMP-activated protein kinase regulation and action in skeletal muscle during exercise. Biochem Soc Trans 31:191–195

    Article  PubMed  CAS  Google Scholar 

  • Nielsen JN, Mustard KJ, Graham DA, Yu H, MacDonald CS, Pilegaard H, Goodyear LJ, Hardie DG, Richter EA, Wojtaszewski JF (2003) 5′AMP-activated protein kinase activity and subunit expression in exercise-trained human skeletal muscle. J Appl Physiol 94:631–641

    PubMed  CAS  Google Scholar 

  • Nielsen JJ, Mohr M, Klarskov K, Kristensen M, Krustrup P, Juel C, Bangsbo J (2004) Effect of high-intensity intermittent training on potassium kinetics and performance in human skeletal muscle. J Physiol 554:857–870

    Article  PubMed  CAS  Google Scholar 

  • Nordsborg N, Bangsbo J, Pilegaard H (2003) Effect of high-intensity training on exercise-induced gene expression specific to ion homeostasis and metabolism. J Appl Physiol 95:1201–1206

    PubMed  CAS  Google Scholar 

  • Pedersen BK, Steensberg A, Fischer C, Keller C, Keller P, Plomgaard P, Fabbraio M, Saltin B (2003) Searching for the exercise factor: is IL-6 a candidate? J Muscle Res Cell Motil 24:113–119

    Article  PubMed  CAS  Google Scholar 

  • Phillips SM, Han XX, Green HJ, Bonen A (1996) Increments in skeletal muscle GLUT-1 and GLUT-4 after endurance training. Am J Physiol 270:E456–E462

    PubMed  CAS  Google Scholar 

  • Pilegaard H, Bangsbo J, Richter EA, Juel C (1994) Lactate transport studied in sarcolemmal giant vesicles from human muscle biopsies—relation to training status. J Appl Physiol 77:1858–1862

    PubMed  CAS  Google Scholar 

  • Pilegaard H, Mohr T, Kjær M, Juel C (1998) Lactate/H+ transport in skeletal muscle from spinal cord injured patients. Scand J Med Sci Sports 8:98–101

    Article  PubMed  CAS  Google Scholar 

  • Pilegaard H, Domino K, Noland T, Juel C, Hellsten Y, Halestrap AP, Bangsbo J (1999a) Effect of high intensity exercise training on lactate/H+ transport capacity in human skeletal muscle. Am J Physiol 276:E225–E261

    Google Scholar 

  • Pilegaard H, Terzis G, Halestrap AP, Juel C (1999b) Distribution of the lactate/H+ transporter isoforms MCT1and MCT4 in human skeletal muscle. Am J Physiol 276:E843–E848

    CAS  Google Scholar 

  • Rennie MJ (2001) How muscle know how to adapt. J Physiol 535:1

    Article  PubMed  CAS  Google Scholar 

  • Rennie MJ, Khogali SE, Low SY, McDowell HE, Hundal HA, Taylor PM (1996) Amino acid transport in heart and skeletal muscle and functional consequences. Biochem Soc Trans 24:869–873

    PubMed  CAS  Google Scholar 

  • Rennie MJ, Low SY, Taylor PM, Khogali SE, Yao PC, Ahmed A (1998) Amino acid transport during muscle contraction and its relevance to exercise. Adv Exp Med Biol 441:299–305

    PubMed  CAS  Google Scholar 

  • Richter EA, Kristiansen S, Wojtaszewski J, Daugaard JR, Asp S, Hespel P, Kiens B (1998) Training effects on muscle glucose transport during exercise. Adv Exp Med Biol 441:107–116

    PubMed  CAS  Google Scholar 

  • Richter EA, Nielsen JN, Jorgensen SB, Frosig C, Birk JB, Wostaszewski JF (2004) Exercise signalling to glucose transport in skeletal muscle. Proc Nutr Soc 63:211–216

    Article  PubMed  CAS  Google Scholar 

  • Snow RJ, Murphy RM (2003) Factors influencing creatine loading into human skeletal muscle. Exerc Sport Sci Rev 31:154–158

    Article  PubMed  Google Scholar 

  • Street D, Bangsbo J, Juel C (2001) Interstitial pH in human skeletal muscle during and after dynamic graded exercise. J Physiol 537:993–998

    Article  PubMed  CAS  Google Scholar 

  • Tabata I, Suzuki Y, Fukunaga Y, Yokozeki T, Akima H, Funato K (1999) Resistance training affect GLUT-4 content in skeletal muscle of humans after 19 days of head-down bed rest. J Appl Physiol 86:909–914

    Article  PubMed  CAS  Google Scholar 

  • Tamai I, Ohashi R, Nezu J, Yabuuchi H, Oku A, Shimane M, Sai Y, Tsuji A (1998) Molecular and functional identification of sodium ion-dependent, high affinity humane carnitine transporter OCTN2. J Biol Chem 273:20378–20382

    Article  PubMed  CAS  Google Scholar 

  • Tarnopolski M, Parise G, Fu MH, Brose A, Parshad A, Speer O, Wallimann T (2003) Acute and moderate-term creatine monohydrate supplementation does not affect creatine transporter mRNA or protein content in either young or elderly humans. Mol Cell Biochem 244:159–166

    Article  PubMed  Google Scholar 

  • Tunstall RJ, Mekan KA Wadley GD, Collier GR, Bonen A, Hargreaves M, Cameron-Smith D (2002) Exercise training increases lipid metabolism gene expression in human skeletal muscle. Am J Physiol 283:E66–E72

    CAS  Google Scholar 

  • Wakayama Y, Jimi T, Inoue M, Kojima H, Shibuya S, Marahashi M, Hara H, Oniki H (2002) Expression of aquaporin 3 and its localization in normal skeletal myofibres. Histochem J 34:331–337

    Article  PubMed  CAS  Google Scholar 

  • Walzer B, Speer O, Boehm E, Kristiansen S, Chan S, Clarke K, Magyar JP, Richter EA, Wallimann T (2002) New creatine transporter assay and identification of distinct creatine transporter isoforms in muscle. Am J Physiol 283:E390–E401

    Google Scholar 

  • Warskulat U, Flogel U, Jacoby C, Hartwig HG, Thewissen M, Merx MW, Molojavyi A, Heller-Stilb B, Schrader J, Haussinger D (2004) Taurine transporter knockout depletes muscle taurine levels and results in severe skeletal muscle impairment but leaves cardiac function uncompromised. FASEB J 18:577–579

    PubMed  CAS  Google Scholar 

  • Wilson MC, Jackson VN, Heddle C, Price NT, Pilegaard H, Juel C, Bonen A, Montgommery I, Hutter OF, Halestrap AP (1998) Lactic acid efflux from white skeletal muscle is catalysed by the monocarboxylate transporter MCT3. J Biol Chem 273:15920–15926

    Article  PubMed  CAS  Google Scholar 

  • Wojtaszewski JF, Richter EA (1998) Glucose utilization during exercise: influence of endurance training. Acta Physiol Scand 162:351–358

    Article  PubMed  CAS  Google Scholar 

  • Wretman C, Lionikas A, Widegren U, Lannergren J, Westerblad H, Henriksson J (2001) Effects of concentric and eccentric contractions on phosphorylation of MAPK (erk1/2) and MAPK (p38) in isolated rat skeletal muscle. J Physiol 535:155–164

    Article  PubMed  CAS  Google Scholar 

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  1. Copenhagen Muscle Research Centre, Institute of Molecular Biology and Physiology, University of Copenhagen, August Krogh Building, Universitetsparken 13, 2100, Copenhagen, Denmark

    Carsten Juel

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Juel, C. Training-induced changes in membrane transport proteins of human skeletal muscle. Eur J Appl Physiol 96, 627–635 (2006). https://doi.org/10.1007/s00421-006-0140-x

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