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. 1998 Jun;74(6):3044–3058. doi: 10.1016/S0006-3495(98)78012-9

ATP analogs and muscle contraction: mechanics and kinetics of nucleoside triphosphate binding and hydrolysis.

M Regnier 1, D M Lee 1, E Homsher 1
PMCID: PMC1299646  PMID: 9635759

Abstract

The mechanical behavior of skinned rabbit psoas muscle fiber contractions and in vitro motility of F-actin (Vf) have been examined using ATP, CTP, UTP, or their 2-deoxy forms (collectively designated as nucleotide triphosphates or NTPs) as contractile substrates. Measurements of actin-activated heavy meromyosin (HMM) NTPase, the rates of NTP binding to myosin and actomyosin, NTP-mediated acto-HMM dissociation, and NTP hydrolysis by acto-HMM were made for comparison to the mechanical results. The data suggest a very similar mechanism of acto-HMM NTP hydrolysis. Whereas all NTPs studied support force production and stiffness that vary by a factor 2 or less, the unloaded shortening velocity (Vu) of muscle fibers varies by almost 10-fold. 2-Deoxy ATP (dATP) was unique in that Vu was 30% greater than with ATP. Parallel behavior was observed between Vf and the steady-state maximum actin-activated HMM ATPase rate. Further comparisons suggest that the variation in force correlates with the rate and equilibrium constant for NTP cleavage; the variations in Vu or Vf are related to the rate of cross-bridge dissociation caused by NTP binding or to the rate(s) of product release.

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Selected References

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  1. Bagshaw C. R., Trentham D. R. The reversibility of adenosine triphosphate cleavage by myosin. Biochem J. 1973 Jun;133(2):323–328. doi: 10.1042/bj1330323. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bagshaw C. R., Trentham D. R. Transient kinetic and isotopic tracer studies of the myosin adenosine triphosphatase reaction. J Supramol Struct. 1975;3(4):315–322. doi: 10.1002/jss.400030402. [DOI] [PubMed] [Google Scholar]
  3. Cecchi G., Griffiths P. J., Taylor S. Stiffness and force in activated frog skeletal muscle fibers. Biophys J. 1986 Feb;49(2):437–451. doi: 10.1016/S0006-3495(86)83653-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chase P. B., Martyn D. A., Hannon J. D. Activation dependence and kinetics of force and stiffness inhibition by aluminiofluoride, a slowly dissociating analogue of inorganic phosphate, in chemically skinned fibres from rabbit psoas muscle. J Muscle Res Cell Motil. 1994 Apr;15(2):119–129. doi: 10.1007/BF00130423. [DOI] [PubMed] [Google Scholar]
  5. Chase P. B., Martyn D. A., Kushmerick M. J., Gordon A. M. Effects of inorganic phosphate analogues on stiffness and unloaded shortening of skinned muscle fibres from rabbit. J Physiol. 1993 Jan;460:231–246. doi: 10.1113/jphysiol.1993.sp019469. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cooke R., Bialek W. Contraction of glycerinated muscle fibers as a function of the ATP concentration. Biophys J. 1979 Nov;28(2):241–258. doi: 10.1016/S0006-3495(79)85174-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cooke R., Pate E. The effects of ADP and phosphate on the contraction of muscle fibers. Biophys J. 1985 Nov;48(5):789–798. doi: 10.1016/S0006-3495(85)83837-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dantzig J. A., Goldman Y. E., Millar N. C., Lacktis J., Homsher E. Reversal of the cross-bridge force-generating transition by photogeneration of phosphate in rabbit psoas muscle fibres. J Physiol. 1992;451:247–278. doi: 10.1113/jphysiol.1992.sp019163. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dantzig J. A., Hibberd M. G., Trentham D. R., Goldman Y. E. Cross-bridge kinetics in the presence of MgADP investigated by photolysis of caged ATP in rabbit psoas muscle fibres. J Physiol. 1991 Jan;432:639–680. doi: 10.1113/jphysiol.1991.sp018405. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Edman K. A. The velocity of unloaded shortening and its relation to sarcomere length and isometric force in vertebrate muscle fibres. J Physiol. 1979 Jun;291:143–159. doi: 10.1113/jphysiol.1979.sp012804. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Eisenberg E., Kielley W. W. Troponin-tropomyosin complex. Column chromatographic separation and activity of the three, active troponin components with and without tropomyosin present. J Biol Chem. 1974 Aug 10;249(15):4742–4748. [PubMed] [Google Scholar]
  12. Ferenczi M. A., Goldman Y. E., Simmons R. M. The dependence of force and shortening velocity on substrate concentration in skinned muscle fibres from Rana temporaria. J Physiol. 1984 May;350:519–543. doi: 10.1113/jphysiol.1984.sp015216. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Fisher A. J., Smith C. A., Thoden J. B., Smith R., Sutoh K., Holden H. M., Rayment I. X-ray structures of the myosin motor domain of Dictyostelium discoideum complexed with MgADP.BeFx and MgADP.AlF4-. Biochemistry. 1995 Jul 18;34(28):8960–8972. doi: 10.1021/bi00028a004. [DOI] [PubMed] [Google Scholar]
  14. Fisher A. J., Smith C. A., Thoden J., Smith R., Sutoh K., Holden H. M., Rayment I. Structural studies of myosin:nucleotide complexes: a revised model for the molecular basis of muscle contraction. Biophys J. 1995 Apr;68(4 Suppl):19S–28S. [PMC free article] [PubMed] [Google Scholar]
  15. Ford L. E., Huxley A. F., Simmons R. M. Tension responses to sudden length change in stimulated frog muscle fibres near slack length. J Physiol. 1977 Jul;269(2):441–515. doi: 10.1113/jphysiol.1977.sp011911. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Fortune N. S., Geeves M. A., Ranatunga K. W. Tension responses to rapid pressure release in glycerinated rabbit muscle fibers. Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7323–7327. doi: 10.1073/pnas.88.16.7323. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Goldman Y. E., Hibberd M. G., Trentham D. R. Relaxation of rabbit psoas muscle fibres from rigor by photochemical generation of adenosine-5'-triphosphate. J Physiol. 1984 Sep;354:577–604. doi: 10.1113/jphysiol.1984.sp015394. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Goldman Y. E., Simmons R. M. Control of sarcomere length in skinned muscle fibres of Rana temporaria during mechanical transients. J Physiol. 1984 May;350:497–518. doi: 10.1113/jphysiol.1984.sp015215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Harada Y., Sakurada K., Aoki T., Thomas D. D., Yanagida T. Mechanochemical coupling in actomyosin energy transduction studied by in vitro movement assay. J Mol Biol. 1990 Nov 5;216(1):49–68. doi: 10.1016/S0022-2836(05)80060-9. [DOI] [PubMed] [Google Scholar]
  20. Hibberd M. G., Dantzig J. A., Trentham D. R., Goldman Y. E. Phosphate release and force generation in skeletal muscle fibers. Science. 1985 Jun 14;228(4705):1317–1319. doi: 10.1126/science.3159090. [DOI] [PubMed] [Google Scholar]
  21. Higuchi H., Takemori S. Butanedione monoxime suppresses contraction and ATPase activity of rabbit skeletal muscle. J Biochem. 1989 Apr;105(4):638–643. doi: 10.1093/oxfordjournals.jbchem.a122717. [DOI] [PubMed] [Google Scholar]
  22. Homsher E., Lacktis J., Regnier M. Strain-dependent modulation of phosphate transients in rabbit skeletal muscle fibers. Biophys J. 1997 Apr;72(4):1780–1791. doi: 10.1016/S0006-3495(97)78824-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Homsher E., Millar N. C. Caged compounds and striated muscle contraction. Annu Rev Physiol. 1990;52:875–896. doi: 10.1146/annurev.ph.52.030190.004303. [DOI] [PubMed] [Google Scholar]
  24. Homsher E., Wang F., Sellers J. R. Factors affecting movement of F-actin filaments propelled by skeletal muscle heavy meromyosin. Am J Physiol. 1992 Mar;262(3 Pt 1):C714–C723. doi: 10.1152/ajpcell.1992.262.3.C714. [DOI] [PubMed] [Google Scholar]
  25. Johnson K. A., Taylor E. W. Intermediate states of subfragment 1 and actosubfragment 1 ATPase: reevaluation of the mechanism. Biochemistry. 1978 Aug 22;17(17):3432–3442. doi: 10.1021/bi00610a002. [DOI] [PubMed] [Google Scholar]
  26. KIELLEY W. W., KALCKAR H. M., BRADLEY L. B. The hydrolysis of purine and pyrimidine nucleoside triphosphates by myosin. J Biol Chem. 1956 Mar;219(1):95–101. [PubMed] [Google Scholar]
  27. Kron S. J., Spudich J. A. Fluorescent actin filaments move on myosin fixed to a glass surface. Proc Natl Acad Sci U S A. 1986 Sep;83(17):6272–6276. doi: 10.1073/pnas.83.17.6272. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Ma Y. Z., Taylor E. W. Kinetic mechanism of myofibril ATPase. Biophys J. 1994 May;66(5):1542–1553. doi: 10.1016/S0006-3495(94)80945-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Margossian S. S., Lowey S. Preparation of myosin and its subfragments from rabbit skeletal muscle. Methods Enzymol. 1982;85(Pt B):55–71. doi: 10.1016/0076-6879(82)85009-x. [DOI] [PubMed] [Google Scholar]
  30. Martyn D. A., Gordon A. M. Force and stiffness in glycerinated rabbit psoas fibers. Effects of calcium and elevated phosphate. J Gen Physiol. 1992 May;99(5):795–816. doi: 10.1085/jgp.99.5.795. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Millar N. C., Homsher E. Kinetics of force generation and phosphate release in skinned rabbit soleus muscle fibers. Am J Physiol. 1992 May;262(5 Pt 1):C1239–C1245. doi: 10.1152/ajpcell.1992.262.5.C1239. [DOI] [PubMed] [Google Scholar]
  32. Millar N. C., Homsher E. The effect of phosphate and calcium on force generation in glycerinated rabbit skeletal muscle fibers. A steady-state and transient kinetic study. J Biol Chem. 1990 Nov 25;265(33):20234–20240. [PubMed] [Google Scholar]
  33. Pate E., Franks-Skiba K., White H., Cooke R. The use of differing nucleotides to investigate cross-bridge kinetics. J Biol Chem. 1993 May 15;268(14):10046–10053. [PubMed] [Google Scholar]
  34. Pate E., Nakamaye K. L., Franks-Skiba K., Yount R. G., Cooke R. Mechanics of glycerinated muscle fibers using nonnucleoside triphosphate substrates. Biophys J. 1991 Mar;59(3):598–605. doi: 10.1016/S0006-3495(91)82275-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Regnier M., Martyn D. A., Chase P. B. Calcium regulation of tension redevelopment kinetics with 2-deoxy-ATP or low [ATP] in rabbit skeletal muscle. Biophys J. 1998 Apr;74(4):2005–2015. doi: 10.1016/S0006-3495(98)77907-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Regnier M., Morris C., Homsher E. Regulation of the cross-bridge transition from a weakly to strongly bound state in skinned rabbit muscle fibers. Am J Physiol. 1995 Dec;269(6 Pt 1):C1532–C1539. doi: 10.1152/ajpcell.1995.269.6.C1532. [DOI] [PubMed] [Google Scholar]
  37. Shimizu T., Furusawa K., Ohashi S., Toyoshima Y. Y., Okuno M., Malik F., Vale R. D. Nucleotide specificity of the enzymatic and motile activities of dynein, kinesin, and heavy meromyosin. J Cell Biol. 1991 Mar;112(6):1189–1197. doi: 10.1083/jcb.112.6.1189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Siemankowski R. F., Wiseman M. O., White H. D. ADP dissociation from actomyosin subfragment 1 is sufficiently slow to limit the unloaded shortening velocity in vertebrate muscle. Proc Natl Acad Sci U S A. 1985 Feb;82(3):658–662. doi: 10.1073/pnas.82.3.658. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Sleep J. A., Hutton R. L. Exchange between inorganic phosphate and adenosine 5'-triphosphate in the medium by actomyosin subfragment 1. Biochemistry. 1980 Apr 1;19(7):1276–1283. doi: 10.1021/bi00548a002. [DOI] [PubMed] [Google Scholar]
  40. Toyoshima Y. Y., Kron S. J., McNally E. M., Niebling K. R., Toyoshima C., Spudich J. A. Myosin subfragment-1 is sufficient to move actin filaments in vitro. Nature. 1987 Aug 6;328(6130):536–539. doi: 10.1038/328536a0. [DOI] [PubMed] [Google Scholar]
  41. Walker J. W., Lu Z., Moss R. L. Effects of Ca2+ on the kinetics of phosphate release in skeletal muscle. J Biol Chem. 1992 Feb 5;267(4):2459–2466. [PubMed] [Google Scholar]
  42. Weber A. Parallel response of myofibrillar contraction and relaxation to four different nucleoside triphophates. J Gen Physiol. 1969 Jun;53(6):781–791. doi: 10.1085/jgp.53.6.781. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. White H. D., Belknap B., Jiang W. Kinetics of binding and hydrolysis of a series of nucleoside triphosphates by actomyosin-S1. Relationship between solution rate constants and properties of muscle fibers. J Biol Chem. 1993 May 15;268(14):10039–10045. [PubMed] [Google Scholar]
  44. White H. D., Belknap B., Webb M. R. Kinetics of nucleoside triphosphate cleavage and phosphate release steps by associated rabbit skeletal actomyosin, measured using a novel fluorescent probe for phosphate. Biochemistry. 1997 Sep 30;36(39):11828–11836. doi: 10.1021/bi970540h. [DOI] [PubMed] [Google Scholar]
  45. White H. D. Special instrumentation and techniques for kinetic studies of contractile systems. Methods Enzymol. 1982;85(Pt B):698–708. doi: 10.1016/0076-6879(82)85057-x. [DOI] [PubMed] [Google Scholar]
  46. White H. D., Taylor E. W. Energetics and mechanism of actomyosin adenosine triphosphatase. Biochemistry. 1976 Dec 28;15(26):5818–5826. doi: 10.1021/bi00671a020. [DOI] [PubMed] [Google Scholar]
  47. Woledge R. C., Curtin N. A., Homsher E. Energetic aspects of muscle contraction. Monogr Physiol Soc. 1985;41:1–357. [PubMed] [Google Scholar]

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