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Myosin light chain phosphorylation is required for peak power output of mouse fast skeletal muscle in vitro

  • Joshua Bowslaugh
  • William Gittings
  • Rene VandenboomEmail author
Muscle physiology

Abstract

The skeletal myosin light chain kinase (skMLCK) catalyzed phosphorylation of the myosin regulatory light chain (RLC) is associated with potentiation of force, work, and power in rodent fast twitch muscle. The purpose of this study was to compare concentric responses of EDL from wild-type (WT) and skMLCK devoid (skMLCK−/−) muscles at a range of shortening speeds (0.05 to 0.70 V max) around that expected to produce maximal power (in vitro, 25 °C) both before (unpotentiated) and after (potentiated) a potentiating stimulus (PS). When collapsed across all speeds tested, neither unpotentiated force, work, or power differed between genotypes (all data n = 10, P < 0.05). In contrast, although both genotypes displayed speed-dependent increases, these increases were greater for WT than skMLCK−/− muscles. For example, when collapsed across the six fastest speeds we tested, both concentric force and power were increased 30–34 % in WT but only 15–17 % in skMLCK−/− muscles. In contrast, at the two slowest speeds, these parameters were increased in WT but decreased in skMLCK−/− muscles (8–10 and 7–9 %, respectively). Intriguingly, potentiation of concentric force and power was optimal near speeds producing maximal power in both genotypes. Because the PS elevated RLC phosphorylation above resting levels in WT but not in skMLCK−/− muscles, our data suggest that skMLCK-catalyzed phosphorylation of the RLC is required for maximal concentric power output of mouse EDL muscle stimulated at high frequency in vitro.

Keywords

Regulatory light chains Length ramps Mean power Extensor digitorum longus Concentric force Work 

Notes

Acknowledgments

This study was supported by funds provided by the Natural Sciences and Engineering Research Council of Canada to R.V. (no. 2014-05122).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Abbate F, Sargeant AJ, Verdijk PW, de Haan A (2000) Effects of high-frequency initial pulses and posttetanic potentiation on power output of skeletal muscle. J Appl Physiol 88:35–40PubMedGoogle Scholar
  2. 2.
    Abbate F, Van Der Velden J, Stienen GJ, De Haan A (2001) Posttetanic potentiation increases energy cost to a higher extent than work in rat fast skeletal muscle. J Musc Res Cell Motil 22:703–710CrossRefGoogle Scholar
  3. 3.
    Abbate F, Bruton JD, De Haan A, Westerblad H (2002) Prolonged force increase following a high-frequency burst is not due to a sustained elevation of [Ca2+]i. Am J Physiol Cell Physiol 283(1):C42–C47CrossRefPubMedGoogle Scholar
  4. 4.
    Alamo L, Qi D, Wriggers W, Pinto A, Zhu J, Bilbao A, Gillilan RE, Hu S, Padron R (2016) Conserved intramolecular interactions maintain myosin interacting-heads motifs explaining tarantula muscle super-relaxed state structural basis. J Mol Biol 428:1142–1164CrossRefPubMedGoogle Scholar
  5. 5.
    Askew GN, Marsh RL (1997) The effects of length trajectory on the mechanical power output of mouse skeletal muscles. J Exp Biol 200(24):3119–3131PubMedGoogle Scholar
  6. 6.
    Askew GN, Marsh RL (1998) Optimal shortening velocity (V/V max) of skeletal muscle during cyclical contractions: length-force effects and velocity-dependent activation and deactivation. J Exp Biol 201(Pt 10):1527–1540PubMedGoogle Scholar
  7. 7.
    Barclay CJ (2005) Modelling diffusive O2 supply to isolated preparations of mammalian skeletal and cardiac muscle. J Musc Res Cell Motil 26:225–235CrossRefGoogle Scholar
  8. 8.
    Brooks SV, Faulkner JA, McCubbrey DA (1990) Power outputs of slow and fast skeletal muscles of mice. J Appl Physiol 68(3):1282–1285CrossRefPubMedGoogle Scholar
  9. 9.
    Brown IE, Loeb GE (1998) Post-activation potentiation: a clue for simplifying models of muscle dynamics. Am Zool 38(4):743–754CrossRefGoogle Scholar
  10. 10.
    Brown IE, Loeb GE (1999) Measured and modeled properties of mammalian skeletal muscle. I. The effects of post-activation potentiation on the time course and velocity dependencies of force production. J Musc Res Cell Motil 20:443–456CrossRefGoogle Scholar
  11. 11.
    Cannell MB (1986) Effect of tetanus duration on the free calcium during the relaxation of frog skeletal muscle fibres. J Physiol 1986(376):203–218CrossRefGoogle Scholar
  12. 12.
    Caputo C, Edman KA, Lou F, Sun YB (1994) Variation in myoplasmic Ca2+ concentration during contraction and relaxation studied by the indicator fluo-3 in frog muscle fibres. J Physiol 478(Pt 1):137–148CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Caterini D, Gittings W, Huang J, Vandenboom R (2011) The effect of work cycle frequency on the potentiation of dynamic function in fast mouse muscle. J Exp Biol 214:3915–3923CrossRefPubMedGoogle Scholar
  14. 14.
    Gittings W, Huang J, Smith I, Quadrilatero J, Vandenboom R (2011) The influence of myosin light chain kinase (MLCK) gene ablation on the contractile performance of skeletal muscles during fatigue. J Musc Res Cell Motil 31:337–348CrossRefGoogle Scholar
  15. 15.
    Gittings W, Huang J, Vandenboom R (2012) Tetanic force potentiation of mouse fast muscle is shortening speed dependent. J Musc Res Cell Motil 33(5):359–368CrossRefGoogle Scholar
  16. 16.
    Gittings W, Aggarwal H, Stull JT, Vandenboom R (2015) The force dependence of isometric and concentric potentiation in mouse muscles with and without myosin light chain kinase. Can J Physiol Pharmacol 93(1):23–32CrossRefPubMedGoogle Scholar
  17. 17.
    Gittings W, Stull JT, Vandenboom R (2016) Interactions between the catch like property and posttetanic potentiation of mouse skeletal muscle. Muscle Nerve 54(2):308–316CrossRefPubMedGoogle Scholar
  18. 18.
    Grange RW, Cory CR, Vandenboom R, Houston ME (1995) Myosin phosphorylation augments the force-displacement and force-velocity relationships of mouse fast muscle. Am J Phys 269:C713–C724Google Scholar
  19. 19.
    Grange RW, Vandenboom R, Xeni J, Houston ME (1998) Potentiation of in vitro concentric work in mouse fast muscle. J Appl Physiol 84:236–243PubMedGoogle Scholar
  20. 20.
    Grange RW, Gainer TG, Marschner KM, Talmadge RJ, Stull JT (2002) Fast-twitch skeletal muscles of dystrophic mouse pups are resistant to injury from acute mechanical stress. Am J Physiol-(Cell Physiol) 283(4):C1090–C1101CrossRefGoogle Scholar
  21. 21.
    James RS, Altringham JD, Goldspink DF (1995) The mechanical properties of fast and slow skeletal muscles of the mouse in relation to their locomotory function. J Exp Biol 198(2):491–502PubMedGoogle Scholar
  22. 22.
    Josephson RK (1999) Dissecting muscle power output. J Exp Biol 202:3369–3375PubMedGoogle Scholar
  23. 23.
    Lannergren J, Bruton JD, Westerblad H (2000) Vacuole formation in fatigued skeletal muscle fibres from frog and mouse: effects of extracellular lactate. J Physiol 526(3):597–611CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Leblond H, L' Esperance M, Orsal D, Rossignol S (2003) Treadmill locomotion in the intact and spinal mouse. J Neurosci 23:11411–11419PubMedGoogle Scholar
  25. 25.
    MacIntosh BR, Bryan SN (2002) Potentiation of shortening and velocity of shortening during repeated isotonic tetanic contractions in mammalian skeletal muscle. Pflugers Arch 443:804–812CrossRefPubMedGoogle Scholar
  26. 26.
    MacIntosh BR, Willis JC (2000) Force-frequency relationship and potentiation in mammalian skeletal muscle. J Appl Physiol 88(6):2088–2096PubMedGoogle Scholar
  27. 27.
    MacIntosh BR, Smith MJ, Rassier DE (2008a) Staircase but not posttetanic potentiation in rat muscle after spinal cord hemisection. Muscle Nerve 38(5):1455–1465CrossRefPubMedGoogle Scholar
  28. 28.
    MacIntosh BR, Taub EC, Dormer GN, Tomaras EK (2008b) Potentiation of isometric and isotonic contractions during high-frequency stimulation. Pflugers Arch 456:449–458CrossRefPubMedGoogle Scholar
  29. 29.
    Mendez J, Keys A (1960) Density and composition of mammalian muscle. Metabolism-Clinical and Experimental 9(2):184–188Google Scholar
  30. 30.
    Patel JR, Diffee GM, Huang XP, Moss RL (1998) Phosphorylation of myosin regulatory light chain eliminates force-dependent changes in relaxation rates in skeletal muscle. Biophys J 74:360–368CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Persechini A, Stull JT, Cooke R (1985) The effect of myosin phosphorylation on the contractile properties of skinned rabbit skeletal muscle fibers. J Biol Chem 260:7951–7954PubMedGoogle Scholar
  32. 32.
    Rassier DE, Tubman LA, MacIntosh BR (1999) Staircase in mammalian muscle without light chain phosphorylation. Braz J Med Biol Res 32(1):121–129CrossRefPubMedGoogle Scholar
  33. 33.
    Ryder JW, Lau KS, Kamm KE, Stull JT (2007) Enhanced skeletal muscle contraction with myosin light chain phosphorylation by a calmodulin-sensing kinase. J Biol Chem 282:20447–20454CrossRefPubMedGoogle Scholar
  34. 34.
    Smith I, Gittings W, Bloemberg D, Huang J, Quadrilatero J, Tupling AR, Vandenboom R (2013) Potentiation in mouse lumbrical muscle without myosin light chain phosphorylation: is resting calcium responsible? J Gen Physiol 141(3):297–308CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Stull JT, Kamm C, Vandenboom R (2011) Myosin light chain kinase and the role of myosin light chain phosphorylation in skeletal muscle. Arch Biochem Biophys 510:120–128CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Tsianos GA, Rustin C, Loeb GE (2012) Mammalian muscle model for predicting force and energetics during physiological behaviors. Neural Systems and Rehabilitation Engineering, IEEE Transactions 20(2):117–133CrossRefGoogle Scholar
  37. 37.
    Vandenboom R, Grange RW, Houston ME (1993) Threshold for force potentiation associated with skeletal myosin phosphorylation. Am J Phys 265(6 Pt 1):C1456–C1462Google Scholar
  38. 38.
    Vandenboom R, Grange RW, Houston ME (1995) Myosin phosphorylation enhances rate of force development in fast-twitch skeletal muscle. Am J Phys 268:596–603Google Scholar
  39. 39.
    Vandenboom R, Xeni J, Bestic M, Houston ME (1997) Increased force development rates of fatigued skeletal muscle are graded to myosin light chain phosphate content. Am J Phys 272:1980–1984Google Scholar
  40. 40.
    Vandenboom R, Gittings W, Smith IC, Grange RW, Stull JT (2013) Myosin phosphorylation and force potentiation in skeletal muscle: evidence from animal models. J Musc Res Cell Motil 34(5–6):317–332CrossRefGoogle Scholar
  41. 41.
    Xeni J, Gittings W, Caterini D, Huang J, Houston ME, Grange RW, Vandenboom R (2011) Myosin light chain phosphorylation and potentiation of dynamic function in mouse fast muscle. Pflugers Archiv 362:349–358CrossRefGoogle Scholar
  42. 42.
    Zhi G, Ryder JW, Huang J, Ding P, Chen Y, Zhao Y, Kamm KE, Stull JT (2005) Myosin light chain kinase and myosin phosphorylation effect frequency-dependent potentiation of skeletal muscle contraction. Proc Natl Acad Sc USA 102:17519–17524CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Joshua Bowslaugh
    • 1
  • William Gittings
    • 1
  • Rene Vandenboom
    • 1
    Email author
  1. 1.Center for Bone and Muscle Health, Faculty of Applied Health SciencesBrock UniversitySt. CatharinesCanada

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