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The role of calcium and calcium/calmodulin-dependent kinases in skeletal muscle plasticity and mitochondrial biogenesis

Published online by Cambridge University Press:  05 March 2007

Eva R. Chin*
Affiliation:
Department of Cardiovascular and Metabolic Diseases, Pfizer Global Research & Development, Eastern Point Rd, MS8220–3120, Groton, CT 06340, USA
*
Corresponding author: Dr Eva R. Chin Fax: +1 860 715 4706, Email: eva_r_chin@groton.pfizer.com
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Abstract

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Intracellular Ca2+plays an important role in skeletal muscle excitation–contraction coupling and also in excitation–transcription coupling. Activity-dependent alterations in muscle gene expression as a result of increased load (i.e. resistance or endurance training) or decreased activity (i.e. immobilization or injury) are tightly linked to the level of muscle excitation. Differential expression of genes in slow- and fast-twitch fibres is also dependent on fibre activation. Both these biological phenomena are, therefore, tightly linked to the amplitude and duration of the Ca2+transient, a signal decoded downstream by Ca2+-dependent transcriptional pathways. Evidence is mounting that the calcineurin–nuclear factor of activated T-cells pathway and the Ca2+/calmodulin-dependent kinases (CaMK) II and IV play important roles in regulating oxidative enzyme expression, mitochondrial biogenesis and expression of fibre-type specific myofibrillar proteins. CaMKII is known to decode frequency-dependent information and is activated during hypertrophic growth and endurance adaptations. Thus, it was hypothesized that CaMKII, and possibly CaMKIV, are down regulated during muscle atrophy and levels of expression of CaMKIIα, -IIβ, -IIγ and -IV were assessed in skeletal muscles from young, aged and denervated rats. The results indicate that CaMKIIγ, but not CaMKIIα or -β, is up regulated in aged and denervated soleus muscle and that CaMKIV is absent in skeletal but not cardiac muscle. Whether CaMKIIγ up-regulation is part of the pathology of wasting or a result of some adaptational response to atrophy is not known. Future studies will be important in determining whether insights from the adaptational response of muscle to increased loads will provide pharmacological approaches for increasing muscle strength or endurance to counter muscle wasting.

Type
Symposium 3: Mechanisms involved in exercise-induced mitochondrial biogenesis in skeletal muscle
Copyright
Copyright © The Nutrition Society 2004

References

Allen, DL & Leinwand, LA (2002) Intracellular calcium and myosin isoform transitions. Calcineurin and calcium-calmodulin kinase pathways regulate preferential activation of the IIa myosin heavy chain promoter. Journal of Biological Chemistry 277, 4532345330.Google Scholar
Allen, DL, Sartorius, CA, Sycuro, LK & Leinwand, LA (2001) Different pathways regulate expression of the skeletal myosin heavy chain genes. Journal of Biological Chemistry 276, 4352443533.Google Scholar
Bayer, KU, Harbers, K & Schulman, H (1998) alphaKAP is an anchoring protein for a novel CaM kinase II isoform in skeletal muscle. EMBO Journal 17, 55985605.Google Scholar
Berchtold, MW, Brinkmeier, H & Muntener, M (2000) Calcium ion in skeletal muscle: its crucial role for muscle function, plasticity, and disease. Physiological Reviews 80, 12151265.CrossRefGoogle Scholar
Braun, AP & Schulman, H (1995) The multifunctional calcium/calmodulin-dependent protein kinase: from form to function. Annual Review of Physiology 57, 417445.CrossRefGoogle Scholar
Chakkalakal, JV, Stocksley, MA, Harrison, MA, Angus, LM, Deschenes-Furry, J, St Pierre, S, Megeney, LA, Chin, ER, Michel, RN & Jasmin, BJ (2003) Expression of utrophin A mRNA correlates with the oxidative capacity of skeletal muscle fiber types and is regulated by calcineurin/NFAT signaling. Proceedings of the National Academy of Sciences USA 100, 77917796.Google Scholar
Chen, G, Carroll, S, Racay, P, Dick, J, Pette, D, Traub, I, Vrbova, G, Eggli, P, Celio, M & Schwaller, B (2001) Deficiency in parvalbumin increases fatigue resistance in fast-twitch muscle and upregulates mitochondria. American Journal of Physiology 281, C114C122.Google Scholar
Chin, ER & Allen, DG (1996) The role of elevations in intracellular [Ca 2+] in the development of low frequency fatigue in mouse single muscle fibres. Journal of Physiology (London) 491, 813824.Google Scholar
Chin, ER, Grange, RW, Viau, F, Simard, AR, Humphries, C, Shelton, J, Bassel-Duby, R, Williams, RS & Michel, RN (2003) Alterations in slow-twitch muscle phenotype in transgenic mice overexpressing the Ca 2+ buffering protein parvalbumin. Journal of Physiology (London) 547, 649663.CrossRefGoogle Scholar
Chin, ER, Olson, EN, Yang, Q, Shelton, J, Bassel-Duby, R & Williams, RS (1998) A calcineurin-dependent pathway controls skeletal muscle fiber type. Genes and Development 12, 24992509.Google Scholar
De Koninck, P & Schulman, H (1998) Sensitivity of CaM kinase II to the frequency of Ca 2+ oscillations. Science 279, 227230.Google Scholar
Dolmetsch, RE, Lewis, RS, Goodnow, CC & Healy, JI (1997) Differential activation of transcription factors induced by Ca 2+ response amplitude and duration. Nature 386, 855858.CrossRefGoogle Scholar
Dunn, SE, Burns, JL & Michel, RN (1999) Calcineurin is required for skeletal muscle hypertrophy. Journal of Biological Chemistry 274, 2190821912.Google Scholar
Flück, M, Waxham, MN, Hamilton, MT & Booth, FW (2000) Skeletal muscle Ca( 2+ )-independent kinase activity increases during either hypertrophy or running. Journal of Applied Physiology 88, 352358.Google Scholar
Freyssenet, D, Di Carlo, M & Hood, DA (1999) Calcium-dependent regulation of cytochrome c gene expression in skeletal muscle cells. Identification of a protein kinase c-dependent pathway. Journal of Biological Chemistry 274, 93059311.Google Scholar
Hennig, R & Lomo, T (1985) Firing patterns of motor units in normal rats. Nature 314, 164166.Google Scholar
Lin, J, Wu, H, Tarr, PT, Zhang, CY, Wu, Z, Boss, O, Michael, LF, Puigserver, P, Isotani, E, Olson, EN, Lowell, BB, Bassel-Duby, R & Spiegelman, BM (2002) Transcriptional co-activator PGC-1 alpha drives the formation of slow-twitch muscle fibres. Nature 418, 797801.Google Scholar
Liu, Y, Cseresnyes, Z, Randall, WR & Schneider, MF (2001) Activity-dependent nuclear translocation and intranuclear distribution of NFATc in adult skeletal muscle fibers. Journal of Cell Biology 155, 2739.Google Scholar
Macpherson, P, Kostrominova, T, Tang, H & Goldman, D (2002) Protein kinase C and calcium/calmodulin-activated protein kinase II (CaMK II) suppress nicotinic acetylcholine receptor gene expression in mammalian muscle. A specific role for CaMK II in activity-dependent gene expression. Journal of Biological Chemistry 277, 1563815646.Google Scholar
Matthews, RP, Guthrie, CR, Wailes, LM, Zhao, X, Means, AR & McKnight, GS (1994) Calcium/calmodulin-dependent protein kinase types II and IV differentially regulate CREB-dependent gene expression. Molecular and Cellular Biology 14, 61076116.Google Scholar
Molkentin, JD, Lu, JR, Antos, CL, Markham, B, Richardson, J, Robbins, J, Grant, SR & Olson, EN (1998) A calcineurin-dependent transcriptional pathway for cardiac hypertrophy. Cell 93, 215228.CrossRefGoogle Scholar
Naya, FJ, Mercer, B, Shelton, J, Richardson, JA, Williams, RS & Olson, EN (2000) Stimulation of slow skeletal muscle fiber gene expression by calcineurin in vivo. Journal of Biological Chemistry 275, 45454548.Google Scholar
Ojuka, EO, Jones, TE, Han, DH, Chen, M & Holloszy, JO (2003) Raising Ca 2+ in L6 myotubes mimics effects of exercise on mitochondrial biogenesis in muscle. FASEB Journal 17, 675681.Google Scholar
Ojuka, EO, Jones, TE, Han, DH, Chen, M, Wamhoff, BR, Sturek, M & Holloszy, JO (2002 a) Intermittent increases in cytosolic Ca 2+ stimulate mitochondrial biogenesis in muscle cells. American Journal of Physiology 283, E1040E1045.Google Scholar
Ojuka, EO, Jones, TE, Nolte, LA, Chen, M, Wamhoff, BR, Sturek, M & Holloszy, JO (2002 b) Regulation of GLUT4 biogenesis in muscle: evidence for involvement of AMPK and Ca( 2+ ). American Journal of Physiology 282, E1008E1013.Google Scholar
Olson, EN & Williams, RS (2000) Remodeling muscles with calcineurin. Bioessays 22, 510519.Google Scholar
Pette, D & Staron, RS (1997) Mammalian skeletal muscle fiber type transitions. International Review of Cytology 170, 143223.Google Scholar
Pette, D & Vrbova, G (1992) Adaptation of mammalian skeletal muscle fibers to chronic electrical stimulation. Reviews in Physiology, Biochemistry and Pharmacology 120, 115202.Google Scholar
Schiaffino, S & Reggiani, C (1996) Molecular diversity of myofibrillar proteins: Gene regulation and functional significance. Physiological Reviews 76, 371423.CrossRefGoogle Scholar
Soderling, TR, Chang, B & Brickey, D (2001) Cellular signaling through multifunctional Ca2+/calmodulin-dependent protein kinase II. Journal of Biological Chemistry 276, 37193722.Google Scholar
Swoap, SJ, Hunter, RB, Stevenson, EJ, Felton, HM, Kansagra, NV, Lang, JM, Esser, KA & Kandarian, SC (2000) The calcineurin-NFAT pathway and muscle fiber-type gene expression. American Journal of Physiology 279, C915C924.CrossRefGoogle Scholar
Vrbova, G (1963) The effects of motoneurone activity on the speed of contraction of striated muscle. Journal of Physiology (London) 169, 513526.Google Scholar
Walke, W, Staple, J, Adams, L, Gnegy, M, Chahine, K & Goldman, D (1994) Calcium-dependent regulation of rat and chick muscle nicotinic acetylcholine receptor (nAChR) gene expression. Journal of Biological Chemistry 269, 1944719456.Google Scholar
Westerblad, H & Allen, DG (1991) Changes in myoplasmic calcium concentration during fatigue in single mouse muscle fibres. Journal of General Physiology 98, 615635.Google Scholar
Wu, H, Kanatous, SB, Thurmond, FA, Gallardo, T, Isotani, E, Bassel-Duby, R & Williams, RS (2002) Regulation of mitochondrial biogenesis in skeletal muscle by CaMK. Science 296, 349352.CrossRefGoogle Scholar
Wu, H, Rothermel, B, Kanatous, S, Rosenberg, P, Naya, FJ, Shelton, JM, Hutcheson, KA, DiMaio, JM, Olson, EN, Bassel-Duby, R & Williams, RS (2001) Activation of MEF2 by muscle activity is mediated through a calcineurin-dependent pathway. EMBO Journal 20, 64146423.Google Scholar
Zong, H, Ren, JM, Young, LH, Pypaert, M, Mu, J, Birnbaum, MJ & Shulman, GI (2002) AMP kinase is required for mitochondrial biogenesis in skeletal muscle in response to chronic energy deprivation. Proceedings of the National Academy of Sciences USA 99, 1598315987.Google Scholar