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Effects of a Myosin-II Inhibitor (N-benzyl-p-toluene Sulphonamide, BTS) on Contractile Characteristics of Intact Fast-twitch Mammalian Muscle Fibres

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Abstract

We have examined the effects of N-benzyl-p-toluene sulphonamide (BTS), a potent and specific inhibitor of fast muscle myosin-II, using small bundles of intact fibres or single fibres from rat foot muscle. BTS decreased tetanic tension reversibly in a concentration-dependent manner with half-maximal inhibition at ∼ ∼2 μM at 20 °C. The inhibition of tension with 10 μM BTS was marked at the three temperatures examined (10, 20 and 30 °C), but greatest at 10 °C. BTS decreased active muscle stiffness to a lesser extent than tetanic tension indicating that not all of the tension inhibition was due to a reduced number of attached cross-bridges. BTS-induced inhibition of active tension was not accompanied by any change in the free myoplasmic Ca2+ transients. The potency and specificity of BTS make it a very suitable myosin inhibitor for intact mammalian fast muscle and should be a useful tool for the examination of outstanding questions in muscle contraction.

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References

  • FH Andrade MB Reid DG Allen H Westerblad (1998) ArticleTitleEffect of hydrogen peroxide and dithiothreitol on contractile function of single skeletal muscle fibres from the mouse J Physiol 509 565–575 Occurrence Handle9575304 Occurrence Handle1:CAS:528:DyaK1cXktlCjtL0%3D

    PubMed  CAS  Google Scholar 

  • MA Bagni G Cecchi B Colombini F Colomo (2002) ArticleTitleA non-cross-bridge stiffness in activated frog muscle fibers Biophys J 82 3118–3127 Occurrence Handle12023235 Occurrence Handle1:CAS:528:DC%2BD38Xkt1Srsro%3D

    PubMed  CAS  Google Scholar 

  • MA Bagni G Cecchi F Colomo P Garzella (1992) ArticleTitleEffects of 2,3-butanedione monoxime on the crossbridge kinetics in frog single muscle fibres J Muscle Res Cell Motil 13 516–522 Occurrence Handle1460080 Occurrence Handle10.1007/BF01737994 Occurrence Handle1:CAS:528:DyaK3sXjs1ejuw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • A Cheung JA Dantzig S Hollingworth SM Baylor YE Goldman TJ Mitchison AF Straight (2002) ArticleTitleA small-molecule inhibitor of skeletal muscle myosin II Nat Cell Biol 4 83–88 Occurrence Handle11744924 Occurrence Handle10.1038/ncb734 Occurrence Handle1:CAS:528:DC%2BD38XhtFGlsbs%3D

    Article  PubMed  CAS  Google Scholar 

  • ME Coupland KW. Ranatunga (2003) ArticleTitleForce generation induced by rapid temperature jumps in intact mammalian (rat) skeletal muscle fibres J Physiol 548 439–449 Occurrence Handle12611915 Occurrence Handle10.1113/jphysiol.2002.037143 Occurrence Handle1:CAS:528:DC%2BD3sXktlCjurs%3D

    Article  PubMed  CAS  Google Scholar 

  • M Fryer I Neering D Stephenson (1988) ArticleTitleEffects of 2,3-butanedione monoxime on the contractile activation properties of fast- and slow-twitch rat muscle fibres J Physiol 407 53–75 Occurrence Handle3256625 Occurrence Handle1:CAS:528:DyaL1cXmt1OmsLo%3D

    PubMed  CAS  Google Scholar 

  • K Horiuti H Higuchi Y Umazume M Konishi O Okazaki S Kurihara (1988) ArticleTitleMechanism of action of 2,3-butanedione 2-monoxime on contraction of frog skeletal muscle fibres J Muscle Res Cell Motil 9 156–164 Occurrence Handle2458382 Occurrence Handle10.1007/BF01773737 Occurrence Handle1:CAS:528:DyaL1cXkvFSntL4%3D

    Article  PubMed  CAS  Google Scholar 

  • A Huxley (1957) ArticleTitleMuscle structure and theories of contraction Prog Biophys 7 258–318

    Google Scholar 

  • AF Huxley RM Simmons (1971) ArticleTitleProposed mechanism of force generation in striated muscle Nature 233 533–538 Occurrence Handle4939977 Occurrence Handle10.1038/233533a0 Occurrence Handle1:CAS:528:DyaE38XjtFehsA%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • M Linari G Piazzesi V Lombardi (2002) ArticleTitleEffects of N-benzyl-p-toluene sulfonamide (BTS) on force and stiffness of active single fibers of frog skeletal muscle Biophys J 82 377

    Google Scholar 

  • DJ Lyster DG Stephenson (1995) ArticleTitleContractile activation and measurements of intracellular Ca2+ concentration in cane toad twitch fibres in the presence of 2,3-butanedione monoxime Exp Physiol 80 543–560 Occurrence Handle7576595 Occurrence Handle1:CAS:528:DyaK2MXnvVamtLc%3D

    PubMed  CAS  Google Scholar 

  • D McKillop M Geeves (1993) ArticleTitleRegulation of the interaction between actin and myosin subfragment 1: evidence for three states of the thin filament Biophys J 65 693–701 Occurrence Handle8218897 Occurrence Handle1:CAS:528:DyaK2cXhsFKqs7k%3D

    PubMed  CAS  Google Scholar 

  • G Mutungi KW Ranatunga (1996) ArticleTitleTension relaxation after stretch in resting mammalian muscle fibers: stretch activation at physiological temperatures Biophys J 70 1432–1438 Occurrence Handle8785299 Occurrence Handle1:CAS:528:DyaK28XitVOgtrw%3D

    PubMed  CAS  Google Scholar 

  • EM Ostap (2002) ArticleTitle2,3-Butanedione monoxime (BDM) as a myosin inhibitor J Muscle Res Cell Motil 23 305–308 Occurrence Handle12630704 Occurrence Handle10.1023/A:1022047102064 Occurrence Handle1:CAS:528:DC%2BD3sXkvFejuw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • G Piazzesi M Reconditi N Koubassova V Decostre M Linari L Lucii V Lombardi (2003) ArticleTitleTemperature dependence of the force-generating process in single fibres from frog skeletal muscle J Physiol (Lond) 549 93–106 Occurrence Handle10.1113/jphysiol.2002.038703 Occurrence Handle1:CAS:528:DC%2BD3sXls1Kls7s%3D

    Article  CAS  Google Scholar 

  • GJ Pinniger KW. Ranatunga (2004a) ArticleTitleA component of stretch induced force in active muscle is not inhibited by BTS (a myosin-II inhibitor) Biophys J 86 565A

    Google Scholar 

  • GJ Pinniger KW Ranatunga (2004b) ArticleTitleEffects of N-benzyl-p-toluene sulphonamide (BTS) on tension responses in intact mammalian skeletal muscle J Physiol 557P C22

    Google Scholar 

  • KW Ranatunga (1999) ArticleTitleEffects of inorganic phosphate on endothermic force generation in muscle Proc Roy Soc Lond (Biol) 266 1381–1385 Occurrence Handle1:CAS:528:DyaK1MXltFyjsrw%3D

    CAS  Google Scholar 

  • MA Shaw EM Ostap YE Goldman (2003) ArticleTitleMechanism of inhibition of skeletal muscle actomyosin by N-benzyl-p-toluene sulfonamide Biochemistry 42 6128–6135 Occurrence Handle12755615 Occurrence Handle10.1021/bi026964f Occurrence Handle1:CAS:528:DC%2BD3sXjtlWit7o%3D

    Article  PubMed  CAS  Google Scholar 

  • DA Smith R Maytum MA Geeves (2003) ArticleTitleCooperative regulation of myosin-actin interactions by a continuous flexible chain I: actin-tropomyosin systems Biophys J 84 3155–3167 Occurrence Handle12719245 Occurrence Handle1:CAS:528:DC%2BD3sXjvFGjuro%3D

    PubMed  CAS  Google Scholar 

  • DA Smith J Sleep (2004) ArticleTitleMechanokinetics of rapid tension recovery in muscle: the myosin working stroke is followed by a slower release of phosphate Biophys J 87 442–456 Occurrence Handle15240478 Occurrence Handle10.1529/biophysj.103.037788 Occurrence Handle1:CAS:528:DC%2BD2cXmtVels70%3D

    Article  PubMed  CAS  Google Scholar 

  • Y-B Sun F Lou KAP Edman (2001) ArticleTitle2,3-Butanedione monoxime increases speed of relaxation in single muscle fibres of frog Acta Physiol Scand 172 53–61 Occurrence Handle11437739 Occurrence Handle10.1046/j.1365-201X.2001.00818.x Occurrence Handle1:CAS:528:DC%2BD3MXltVKgsbw%3D

    Article  PubMed  CAS  Google Scholar 

  • A Tripathy L Xu DA Pasek G Meissner (1999) ArticleTitleEffects of 2,3-butanedione 2-monoxime on Ca2+ release channels (ryanodine receptors) of cardiac and skeletal muscle J Membr Biol 169 189–198 Occurrence Handle10354465 Occurrence Handle10.1007/s002329900530 Occurrence Handle1:CAS:528:DyaK1MXjvF2ru70%3D

    Article  PubMed  CAS  Google Scholar 

  • IS Young CL Harwood LC Rome (2003) ArticleTitleCross-bridge blocker BTS permits direct measurement of SR Ca2+ pump ATP utilization in toadfish swimbladder muscle fibers Am J Physiol Cell Physiol 285 C781–787 Occurrence Handle12773313 Occurrence Handle1:CAS:528:DC%2BD3sXosV2rt7c%3D

    PubMed  CAS  Google Scholar 

  • Y Zhao M Kawai (1994) ArticleTitleKinetic and thermodynamic studies of the cross-bridge cycle in rabbit psoas muscle fibers Biophys J 67 1655–1668 Occurrence Handle7819497 Occurrence Handle1:CAS:528:DyaK2cXmt1Ogtb4%3D Occurrence Handle10.1016/S0006-3495(94)80638-1

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Muscle Contraction Group, Department of Physiology, School of Medical Sciences, University of Bristol, Bristol, BS8 1TD, UK

    G. J. Pinniger & K. W. Ranatunga

  2. Department of Physiology and Pharmacology, Karolinska Institute, 171 77, Stockholm, Sweden

    J. D. Bruton & H. Westerblad

Authors
  1. G. J. Pinniger
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  2. J. D. Bruton
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  3. H. Westerblad
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  4. K. W. Ranatunga
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Correspondence to G. J. Pinniger.

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Pinniger, G.J., Bruton, J.D., Westerblad, H. et al. Effects of a Myosin-II Inhibitor (N-benzyl-p-toluene Sulphonamide, BTS) on Contractile Characteristics of Intact Fast-twitch Mammalian Muscle Fibres. J Muscle Res Cell Motil 26, 135–141 (2005). https://doi.org/10.1007/s10974-005-2679-2

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  • DOI: https://doi.org/10.1007/s10974-005-2679-2

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