Mitochondrial Ca2+ in Mouse Soleus Single Muscle Fibres in Response to Repeated Tetanic Contractions

  • Jan Lännergren
  • Joseph D. Bruton
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 538)


Mitochondrial diseases form a heterogeneous group of disorders in which mutations of the mitochondrial material frequently results in muscle dysfunction. Mammalian skeletal muscle fibres are particularly rich in mitochondria, which may make up about 10 to 15 % of a fibre’s volume (Eisenberg, 1983; Chen et al., 2001). Mitochondria are differentially distributed in many rodent skeletal muscles, with a higher density found close to the sarcolemma than deep in the fibre (Eisenberg et al., 1983; Philippi & Sillau, 1994). It has long been accepted that a key function of mitochondria is to supply energy as required by the working muscle. (1990) proposed that Ca2+ plays a key role in this process by activating three key mitochondrial dehydrogenases. More recently, a rise in mitochondrial Ca2+ was suggested to directly stimulate mitochondrial oxidative phosphorylation (Kavanagh et al., 2000). While circumstantial evidence suggests that mitochondria in skeletal muscle are able to modulate their Ca2+ content, surprisingly little is know about Ca2+ movement into and out of the mitochondria in intact skeletal muscle cells during and after a bout of contractile activity. Several groups have reported that mitochondria isolated from skeletal muscle after exhaustive exercise have a higher Ca2+ content than those obtained from non-exercised muscle (Duan et al., 1990; Madsen et al., 1996). Other groups have reported that mitochondria are swollen or disrupted in skeletal muscle isolated from animals that were exercised to exhaustion, (Gollnick & King, 1969; McCutcheon et al., 1992; Sakai et al., 1999).


Skeletal Muscle Soleus Muscle Mammalian Skeletal Muscle Skeletal Muscle Mitochondrion Soleus Fibre 
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  1. Babcock, D.F., Herrington, J., Goodwin, P.C., Park, Y.B., and Hille, B., 1997, Mitochondrial participation in the intracellular Ca2+ network. J. Cell Biol. 136: 833–844.PubMedCrossRefGoogle Scholar
  2. Butinas, L, Gunter, K.L., Sparagna, G.C., and Gunter, T.E., 2001, The rapid mode of calcium uptake into heart mitochondria (RaM): comparison to RaM in liver mitochondria. Biochim. Biophys. Acta 1504: 248–261.CrossRefGoogle Scholar
  3. Chen, G., Carroll, S., Racay, P., Dick, J., Pette, D., Traub, I., Vrbova, G., Eggli, P., Celio, M, and Schwaller, B., 2001, Deficiency in parvalbumin increases fatigue resistance in fast-twitch muscle and upregulates mitochondria. Am. J. Physiol. 281: Cl 14–C122.Google Scholar
  4. David, G., Barrett, J.N., and Barrett, E.F., 1998, Evidence that mitochondria buffer physiological Ca2+ loads in lizard motor nerve terminals. J. Physiol. 509: 59–65.PubMedCrossRefGoogle Scholar
  5. Denton, R.M., and McCormack, J.G., 1990, Ca2+ as a second messenger within mitochondria of the heart and other tissue. Ann. Rev. Physiol. 52: 451–466.CrossRefGoogle Scholar
  6. Duan, C, Delp, MD., Hayes, D.A., Delp, P.D., and Armstrong, R.B., 1990, Rat skeletal muscle mitochondrial [Ca2+] and injury from downhill walking. J.Appl. Physiol. 68: 1241–1251.PubMedGoogle Scholar
  7. Duchen, MR., Leyssens, A., and Crompton, M., 1998, Transient mitochondrial depolarizations reflect focal sarcoplasmic reticular calcium release in single rat cardiomyocytes. J. Cell Biol. 142:975–988.PubMedCrossRefGoogle Scholar
  8. Dykens, J.A., 1994, Isolated cerebral and cerebellar mitochondria produce free radicals when exposed to elevated Ca2+ and Na+: implications for neurodegeneration. J. Neurochem. 63: 584–591.PubMedCrossRefGoogle Scholar
  9. Eisenberg, B.A., 1983, Quantitative ultrastructure of mammalian skeletal muscle. In: Handbook of Physiology-Skeletal Muscle, L.D. Peachey, ed., American Physiological Society, Bethesda MD, pp 73–112.Google Scholar
  10. Gillis, J.M., 1997, Inhibition of mitochondrial calcium uptake slows down relaxation in mitochondria-rich skeletal muscles. J. Muscle Res. Cell Motil 18: 473–483.PubMedCrossRefGoogle Scholar
  11. Gollnick, P.D. & King, D.W., 1969, Effect of exercise and training on mitochondria of rat skeletal muscle. Am. J. Physiol. 216:1502–1509.PubMedGoogle Scholar
  12. Grijalba, MT., Vercesi, A.E., and Schreier, S., 1999, Ca2+-induced increased lipid packing and domain formation in submitochondrial particles. A possible early step in the mechanism of Ca2+-stimulated generation of reactive oxygen species by the respiratory chain. Biochem. 38: 13279–13287.CrossRefGoogle Scholar
  13. Harris, E.J., 1978, Anion/calcium ion ratios and proton production in some mitochondrial calcium ion uptakes. Biochem. J. 176:983–991.PubMedGoogle Scholar
  14. He, L, and Lemasters, J.J., 2002, Regulated and unregulated mitochondrial permeability transition pores: a new paradigm of pore structure and function? FEBS Lett. 512:1–7.PubMedCrossRefGoogle Scholar
  15. Hood, D.A., 2001, Invited Review: contractile activity-induced mitochondrial biogenesis in skeletal muscle. J. Appl. Physiol. 90: 1137–1157.PubMedGoogle Scholar
  16. Jouaville, L.S., Pinton, P., Bastianutto, C, Rutter, G.A., and Rizzuto, R., 1999, Regulation of mitochondrial ATP synthesis by calcium: evidence for a long-term metabolic priming. Proc. Nat. Acad. Sci. USA 96: 13807–13812.PubMedCrossRefGoogle Scholar
  17. Joyal, J.L., Hagen, T., and Aprille, J.R., 1995, Intramitochondrial protein synthesis is regulated by matrix adenine nucleotide content and requires calcium. Arch. Biochem. Biophys. 319: 322–330.PubMedCrossRefGoogle Scholar
  18. Kavanagh, N.I., Ainscow, E.K., and Brand, MD., 2000, Calcium regulation of oxidative phosphorylation in rat skeletal muscle mitochondria. Biochim. Biophys. Acta 1457: 57–70.PubMedCrossRefGoogle Scholar
  19. Lännergren, J., Westerblad, H., and Bruton, J.D., 2001, Changes in mitochondrial Ca2+ detected with Rhod-2 in single frog and mouse skeletal muscle fibres during and after repeated tetanic contractions. J. Muscle Res. Cell Motil. 22: 265–275.PubMedCrossRefGoogle Scholar
  20. Lestienne, P., Bataille, N., and Lucas-Heron, B., 1995, Role of the mitochondrial DNA and calmitine in myopathies. Biochim. Biophys. Acta 1271: 159–163. myopathies. Biochim. Biophys. Acta 1271: 159-163.PubMedCrossRefGoogle Scholar
  21. Ligeti, E., and Lukacs, G.L., 1984, Phosphate transport, membrane potential, and movements of calcium in rat liver mitochondria. J. Bioenerg. Biomembr. 16: 101–113.PubMedCrossRefGoogle Scholar
  22. Litsky, M.L., and Pfeiffer, D.R., 1997, Regulation of the mitochondrial Ca2+ uniporter by external adenine nucleotides: the uniporter behaves like a gated channel which is regulated by nucleotides and divalent cations. Biochem. 36: 7071–7080.CrossRefGoogle Scholar
  23. Lucas-Heron, B., Le Ray, B., and Schmitt, N., 1995, Does calmitine, a protein specific for the mitochondrial matrix of skeletal muscle, play a key role in mitochondrial function? FEBS Lett. 374: 309–311.PubMedCrossRefGoogle Scholar
  24. Madsen, K., Ertbjerg, P., Djurhuus, M.S., and Pedersen, P.K., 1996, Calcium content and respiratory control index of skeletal muscle mitochondria during exercise and recovery. Am. J. Physiol. 271: E1044–E1050.PubMedGoogle Scholar
  25. Marechal, G., and Beckers-Bleukx, G., 1993, Force-velocity relation and isomyosins in soleus muscles from two strains of mice (C57 and NMRI). Pflüg. Arch. 424: 478–487.CrossRefGoogle Scholar
  26. Milner, D.J., Mavroidis, M., Weisleder, N., and Capetanaki Y., 2000, Desmin cytoskeleton linked to muscle mitochondrial distribution and respiratory function. J. Cell Biol. 150: 1283–1298.PubMedCrossRefGoogle Scholar
  27. McCutcheon, L.J., Byrd, S.K., and Hodgson; D.R., 1992, Ultrastructural changes in skeletal muscle after fatiguing exercise. J. Appl. Physiol. 72: 1111–1117.PubMedGoogle Scholar
  28. Philippi, M., and & Sillau, A.H., 1994, Oxidative capacity distribution in skeletal muscle fibres of the rat J. Exp. Biol. 189:1–11.PubMedGoogle Scholar
  29. Reid, M.B., and Durham, W.J., 2002, Generation of reactive oxygen and nitrogen species in contracting skeletal muscle. Ann. New York Acad. Sci. 959: 108–116.CrossRefGoogle Scholar
  30. Rizzuto, R., Pinton, P., Brini, M., Chiesa, A., Filippin, L, and Pozzan, T., 1999, Mitochondria as biosensors of calcium microdomains. Cell Calcium 26: 193–199.PubMedCrossRefGoogle Scholar
  31. Sakai, Y., Iwarmura, Y., Hayashi, J.I., Yamamoto, N., Ohkoshi, N., and Nagata, H., 1999, Acute exercise causes mitochondiral DNA deletion in rat skeletal muscle. Muscle Nerve 22: 268–261.CrossRefGoogle Scholar
  32. Sembrowich, W.L., Quintinskie, J.J., and Li, G., 1985, Calcium uptake in mitochondria from different skeletal muscle types. J. Appl. Physiol. 59: 137–141.PubMedGoogle Scholar
  33. Sparagna, G.C., Gunter, K.K., Sheu, S.S., and Gunter, T.E., 1995, Mitochondrial calcium uptake from physiological-type pulses of calcium: a description of the rapid uptake mode. J. Biol. Chem. 270: 27510–27515.PubMedCrossRefGoogle Scholar
  34. Walsh, B., Tonkonogi, M., Soderlund, K., Hultman, E., Saks, V., and Sahlin, K., 2001, The role of phosphorylcreatine and creatine in the regulation of mitochondrial respiration in human skeletal muscle. J. Physiol. 537: 971–978.PubMedCrossRefGoogle Scholar
  35. Wu, H., Kanatous, S.B., Thurmond, F. A, Gallardo, T., Isotani, E., Bassel-Duby, R., and Williams, R.S., 2002, Regulation of mitochondrial biogenesis in skeletal muscle by CaMK. Science 296: 349–352.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2003

Authors and Affiliations

  • Jan Lännergren
  • Joseph D. Bruton
    • 1
  1. 1.Department of Physiology and PharmacologyKarolinska InstitutedStockholmSweden

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