Skip to main content
SpringerLink
Log in

Posttetanic potentiation in mdx muscle

  • Original Paper
  • Published:
Journal of Muscle Research and Cell Motility Aims and scope Submit manuscript

Abstract

X-linked muscular dystrophy of the mouse (mdx) has been reported to progressively remodel skeletal muscle to preferentially reduce fast fiber composition. Despite this, mdx muscle displays normal levels of posttetanic potentiation (PTP). Since PTP may primarily depend on phosphorylation of the myosin regulatory light chain (RLC) in fast muscle fibers, maintenance of PTP with mdx disease progression is paradoxical and may represent an adaptation of the diseased muscle. This study assesses the role of RLC phosphorylation during PTP of mdx muscle. Extensor digitorum longus muscles were isolated from mdx and from C57BL/10 (control) mice at ~50 (young) and ~300 (adult) days and stimulated in vitro (25°C) to induce PTP. During potentiation, muscles were harvested for subsequent determination of RLC phosphorylation levels. Immunofluorescence was used to assess muscle fiber type composition and no age effects were found. The magnitude of PTP was higher (P < 0.05) in mdx than control muscles at both young (mdx: 21.9 ± 1.6%; control: 17.7 ± 1.2%) and adult (mdx: 30.4 ± 1.8%; control: 23.2 ± 2.2%) ages. However, RLC phosphate content was similar between all groups both at rest and following stimulation. Our results are consistent with a model where the sensitivity of mdx muscle to RLC phosphorylation-induced force potentiation is increased by disease- and age-dependent alterations in excitation-contraction coupling noted for mdx and aging muscle.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Abbreviations

½RT:

Half relaxation time

AC:

Adult control

AM:

Adult mdx

CS:

Conditioning stimulus

CSA:

Cross sectional area

EDL:

Extensor digitorum longus

ICT:

Intracellular calcium transient

Lo :

Optimal length for twitch tension development

mdx :

X-linked muscular dystrophy

MHC:

myosin heavy chain

PTP:

Posttetanic potentiation

RLC:

Regulatory light chain

skMLCK:

Skeletal muscle isoform of myosin light chain kinase

TPT:

Time to peak tension

YC:

Young control

YM:

Young mdx

References

  • Anderson JE, Bressler BH, Ovalle WK (1988) Functional regeneration in the hindlimb skeletal muscle of the mdx mouse. J Muscle Res Cell Motil 9:499–515

    Article  CAS  PubMed  Google Scholar 

  • Brown IA, Loeb GE (1998) Post-activation potentiation: a clue for simplifying models of muscle dynamics. Am Zool 38:743–754

    Google Scholar 

  • Bulfield G, Siller WG, Wight PAL, Moore KJ (1984) X chromosome-linked muscular dystrophy (mdx) in the mouse. Proc Natl Acad Sci USA 81:1189–1192

    Article  CAS  PubMed  Google Scholar 

  • Close R, Hoh JF (1969) Post-tetanic potentiation of twitch contractions of cross-innervated rat fast and slow muscles. Nature 221:179–181

    Article  CAS  PubMed  Google Scholar 

  • Coirault C, Lambert F, Marchand-Adam S, Attal P, Chemla D, Lecarpentier Y (1999) Myosin molecular motor dysfunction in dystrophic mouse diaphragm. Am J Physiol 277:C1170–C1176

    CAS  PubMed  Google Scholar 

  • Coirault C, Lambert F, Pourny JC, Lecarpentier Y (2002) Velocity of actomyosin sliding in vitro is reduced in dystrophic mouse diaphragm. Am J Respir Crit Care Med 165(2):250–253

    PubMed  Google Scholar 

  • DiMario JX, Uzman A, Strohman RC (1991) Fiber regeneration is not persistent in dystrophic (mdx) mouse skeletal muscle. Dev Biol 148:314–321

    Article  CAS  PubMed  Google Scholar 

  • González E, Messi ML, Zheng Z, Delbono O (2003) Insulin-like growth factor-1 prevents age-related decrease in specific force and intracellular Ca2+ in single intact muscle fibres from transgenic mice. J Physiol 552:833–844

    Article  PubMed  Google Scholar 

  • Hayes A, Williams DA (1996) Beneficial effects of voluntary wheel running on the properties of dystrophic mouse muscle. J Appl Physiol 80:670–679

    CAS  PubMed  Google Scholar 

  • Hollingworth S, Zeiger U, Baylor SM (2008) Comparison of the myoplasmic calcium transient elicited by an action potential in intact fibres of mdx and normal mice. J Physiol 586:5063–5075

    Article  CAS  PubMed  Google Scholar 

  • Hopf FW, Turner PR, Denetclaw WF, Reddy P, Steinhardt RA (1996) A critical evaluation of resting intracellular free calcium regulation in dystrophic mdx muscle. Am J Physiol 271:C1325–C1339

    CAS  PubMed  Google Scholar 

  • Kamm KE, Hsu LC, Kubota Y, Stull JT (1989) Phosphorylation of smooth muscle myosin heavy and light chains. J Biol Chem 264:21223–21229

    CAS  PubMed  Google Scholar 

  • Klug GA, Botterman BR, Stull JT (1982) The effect of low frequency stimulation on myosin light chain phosphorylation in skeletal muscle. J Biol Chem 257:4688–4690

    CAS  PubMed  Google Scholar 

  • Krarup C (1981) Enhancement and diminution of mechanical tension evoked by staircase and by tetanus in rat muscle. J Physiol 311:355–372

    CAS  PubMed  Google Scholar 

  • Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685

    Article  CAS  PubMed  Google Scholar 

  • Lamb GD, Junankar PR, Stephenson DG (1995) Raised intracellular [Ca2+] abolishes excitation-contraction coupling in skeletal muscles of rat and toad. J Physiol 489:349–362

    CAS  PubMed  Google Scholar 

  • Landisch RM, Kosir AM, Nelson SA, Baltgalvis KA, Lowe DA (2008) Adaptive and nonadaptive responses to voluntary wheel running by mdx mice. Muscle Nerve 38(4):1290–1303

    Article  PubMed  Google Scholar 

  • Lännergren J, Westerblad H (1987) The temperature dependence of isometric contractions of single, intact fibres dissected from a mouse foot muscle. J Physiol 390:285–293

    PubMed  Google Scholar 

  • Lännergren J, Bruton JD, Westerblad H (2000) Vacuole formation in fatigued skeletal muscle fibres from frog and mouse: effects of extracellular lactate. J Physiol 526:597–611

    Article  PubMed  Google Scholar 

  • Louboutin JP, Fichter-Gagnepain V, Thaon E, Fardeau M (1993) Morphometric analysis of mdx diaphram muscle fibres. Comparison with hindlimb muscles. Neuromuscul Disord 3(5–6):463–469

    Article  CAS  PubMed  Google Scholar 

  • Louboutin JP, Fichter-Gagnepain V, Pastoret C, Thaon E, Noireaud J, Sébille A, Fardeau M (1995) Morphological and functional study of extensor digitorum longus muscle regeneration after iterative crush lesions in mdx muscle. Neuromuscul Disord 5:489–500

    Article  CAS  PubMed  Google Scholar 

  • Lynch GS, Hinkle RT, Chamberlain JS, Brooks SV, Faulkner JA (2001) Force and power output of fast and slow skeletal muscles from mdx mice 6–28 months old. J Physiol 535:591–600

    Article  CAS  PubMed  Google Scholar 

  • Mallouk N, Jacquemond V, Allard B (2000) Elevated subsarcolemmal Ca2+ in mdx mouse skeletal muscle fibers detected with Ca2+-activated K(+) channels. Proc Natl Acad Sci USA 97:4950–4955

    Article  CAS  PubMed  Google Scholar 

  • Manning DR, Stull JT (1982) Myosin light chain phosphorylation-dephosphorylation in mammalian skeletal muscle. Am J Physiol 242:C234–C241

    CAS  PubMed  Google Scholar 

  • Mechalchuk CL, Bressler BH (1992) Contractility of mdx skeletal muscle after denervation and devascularization. Muscle Nerve 15:310–317

    Article  CAS  PubMed  Google Scholar 

  • Mendez J, Keys A (1960) Density and composition of mammalian muscle. Metabolism 9:184–199

    CAS  Google Scholar 

  • Moore RL, Stull JT (1984) Myosin light chain phosphorylation in fast and slow skeletal muscles in situ. Am J Physiol 247:C462–C471

    CAS  PubMed  Google Scholar 

  • Moore RL, Palmer BM, Williams SL, Tanabe H, Grange RW, Houston ME (1990) Effect of temperature on myosin phosphorylation in mouse skeletal muscle. Am J Physiol 259:C432–C438

    CAS  PubMed  Google Scholar 

  • Palmer B, Moore R (1989) Myosin light chain phosphorylation and tension potentiation in mouse skeletal muscle. Am J Physiol 257:C1012–C1019

    CAS  PubMed  Google Scholar 

  • Payne AM, Jiménez-Moreno R, Wang ZM, Messi ML, Delbono O (2009) Role of Ca2+, membrane excitability, and Ca2+ stores in failing muscle contraction with aging. Exp Gerontol 44:261–273

    Article  CAS  PubMed  Google Scholar 

  • 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 260:7951–7954

    CAS  PubMed  Google Scholar 

  • Petrof BJ, Shrager JB, Stedman HH, Kelly AM, Sweeney HL (1993a) Dystrophin protects the sarcolemma from stresses developed during muscle contraction. Proc Natl Acad Sci USA 90:3710–3714

    Article  CAS  PubMed  Google Scholar 

  • Petrof BJ, Stedman HH, Shrager JB, Eby J, Sweeney HL, Kelly AM (1993b) Adaptations in myosin heavy chain expression and contractile function in dystrophic mouse diaphragm. Am J Physiol 265:C834–C841

    CAS  PubMed  Google Scholar 

  • Quinlan JG, Johnson SR, McKee MK, Lyden SP (1992) Twitch and tetanus in mdx mouse muscle. Muscle Nerve 15:837–842

    Article  CAS  PubMed  Google Scholar 

  • Ribaux P, Bleicher F, Couble ML, Amsellem J, Cohen SA, Berthier C, Blaineau S (2001) Voltage-gated sodium channel (SkM1) content in dystrophin-deficient muscle. Pflugers Arch 441:746–755

    Article  CAS  PubMed  Google Scholar 

  • Rousseau J, Dumont N, Lebel C, Quenneville SP, Côté CH, Frenette J, Tremblay JP (2010) Dystrophin expression following the transplantation of normal muscle precursor cells protects mdx muscle from contraction induced damage. Cell Transplant 19(5):589–596

    Article  PubMed  Google Scholar 

  • 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 282:20447–20454

    Article  CAS  PubMed  Google Scholar 

  • Sacco P, Jones DA, Dick JR, Vrbova G (1992) Contractile properties and susceptibility to exercise-induced damage of normal and mdx mouse tibialis anterior muscle. Clin Sci (Lond) 82:227–236

    CAS  Google Scholar 

  • Schacterle GR, Pollack RL (1973) A simplified method for the quantitative assay of small amounts of protein in biologic material. Anal Biochem 51:654–655

    Article  CAS  PubMed  Google Scholar 

  • Sweeney HL, Stull JT (1986) Phosphorylation of myosin in permeablized mammalian cardiac and skeletal muscle cells. Am J Physiol 250:C657–C660

    CAS  PubMed  Google Scholar 

  • Sweeney HL, Bowman BM, Stull JT (1993) Myosin light chain phosphorylation in vertebrate striated muscle: regulation and function. Am J Physiol 264:C1085–C1095

    CAS  PubMed  Google Scholar 

  • Turner PR, Westwood T, Regen CM, Steinhardt RA (1988) Increased protein degradation results from elevated free calcium levels found in muscle from mdx mice. Nat Lond 335:735–738

    Article  CAS  Google Scholar 

  • Vandenboom R, Xeni J, Bestic NM, Houston ME (1997) Increased force development rates of fatigued mouse skeletal muscle are graded to myosin light chain phosphate content. Am J Physiol 272:R1980–R1984

    CAS  PubMed  Google Scholar 

  • Wang ZM, Messi ML, Delbono O (2000) L-Type Ca(2+) channel charge movement and intracellular Ca(2+) in skeletal muscle fibers from aging mice. Biophys J 78:1947–1954

    Article  CAS  PubMed  Google Scholar 

  • Wolff AV, Niday AK, Voelker KA, Call JA, Evans NP, Granata KP, Grange RW (2006) Passive mechanical properties of maturing extensor digitorum longus are not affected by lack of dystrophin. Muscle Nerve 34:304–312

    Article  CAS  PubMed  Google Scholar 

  • 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 Sci USA 102:17519–17524

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by funds provided by the Natural Sciences and Engineering Research Council of Canada. I.C. Smith was funded through a Masters Studentship from the Canadian Institutes of Health Research. We would like to thank Dr. Jim Stull for his assistance in the analysis of the myosin RLC phosphate content.

Conflict of interest

The authors do not have any conflicting interests regarding the findings or interpretations of this manuscript.

Author information

Authors and Affiliations

  1. Center for Muscle Metabolism and Biophysics, Brock University, St. Catharines, ON, Canada

    Ian Curtis Smith & Rene Vandenboom

  2. University of Texas, Southwestern Texas Medical Center Dallas, Dallas, TX, USA

    Jian Huang

  3. Department of Kinesiology, University of Waterloo, Waterloo, ON, Canada

    Joe Quadrilatero & Allan Russell Tupling

  4. Department of Physical Education and Kinesiology, Brock University, 500 Glenridge Ave, St. Catharines, ON, L2S 3A1, Canada

    Rene Vandenboom

Authors
  1. Ian Curtis Smith
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jian Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Joe Quadrilatero
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Allan Russell Tupling
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rene Vandenboom
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rene Vandenboom.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Smith, I.C., Huang, J., Quadrilatero, J. et al. Posttetanic potentiation in mdx muscle. J Muscle Res Cell Motil 31, 267–277 (2010). https://doi.org/10.1007/s10974-010-9229-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10974-010-9229-2

Keywords

Search

Navigation