A Chemical Mechanism for Excitation-Contraction Coupling in Skeletal Muscle

  • Julio Vergara
  • Nestor Lagos
  • Deida Compagnon
Part of the Series of the Centro de Estudios Científicos de Santiago book series (SCEC)


The early process of excitation-contraction coupling in skeletal muscle primarily involves the participation of a network of transverse tubules (T-tubules) and a coupling structure at which the T-tubular membrane encounters the sarcoplasmic reticulum (SR) membrane (T-SR junction). The transverse tubular system (T-system) is open to the extracellular space and connects with the surface membrane where the action potential propagates along the fiber. Currently it is known that the action potential also propagates radially into the deepest regions of the T-system(1–4) and that somehow the electrical activation of the T-system membrane promotes the release of Ca2 + from the SR membrane(1,5–8) which is about 20 nm apart(9) There are three models proposing mechanisms to explain the coupling at the T-SR junction in skeletal muscle that are currently considered: (i) The Ca2+ -induced Ca2+ release hypothesis (10,11) suggests that an entry of Ca2+ ions from the extracellular space results in an amplified release from the SR. (ii) The direct coupling hypothesis implies that the depolarization of the T-system membranes initiates a perturbation that mechanically propagates across the 20 nm gap to induce the release of Ca2+ from the SR(12) (iii) The chemical coupling hypothesis(13) states that the depolarization of the T-system membrane modulates the synthesis of a chemical transmitter (IP3), which diffuses across the gap, binds to a postjunctional receptor (Ca2+ -channel), and induces the release of Ca2+ from the SR.(13,14)


Sarcoplasmic Reticulum Skeletal Muscle Fiber Charge Movement Single Muscle Fiber Frog Skeletal Muscle 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Huxley, A. F., and Taylor, R. E., 1958, Local activation of striated muscle fibers. J. Physiol. (London). 144: 426–451.Google Scholar
  2. 2.
    Adrian, R. H., Chandler, W. K., and Hodgkin, A. L., 1969, The kinetics of mechanical activation in frog muscle, J. Physiol. (London) 204: 207–230.Google Scholar
  3. 3.
    Adrian, R. H., Costantin, L. L., and Peachey, L. D., 1969, Radial spread of contraction in frog muscle fibers, J. Physiol. (London) 204: 231–257.Google Scholar
  4. 4.
    Heiny, J. A., and Vergara, J., 1982, Optical signals from surface and T-system membranes in skeletal muscle fibers, J. Gen. Physiol. 80: 203–230.PubMedCrossRefGoogle Scholar
  5. 5.
    Hodgkin, A. L., and Horowicz, P., 1960, Potassium contractures in single muscle fibers, J. Physiol. (London) 153: 386–403.Google Scholar
  6. 6.
    Kovacs, L., Rios, E., and Schneider, M. F., 1979, Calcium transients and intramembrane charge movement in skeletal muscle fibers, Nature (London) 279: 391–396.CrossRefGoogle Scholar
  7. 7.
    Baylor, S. M., Chandler, W. K., and Marshall, M. W., 1983, Sarcoplasmic reticulum calcium release in frog skeletal muscle fibers estimated from arsenazo III calcium transients, J. Physiol. (London) 344: 625–666.Google Scholar
  8. 8.
    Palade, P., and Vergara, J., 1982, Arsenazo III and antipyrylazo III calcium transients in single skeletal muscle fibers, J. Gen. Physiol. 79: 679–707.PubMedCrossRefGoogle Scholar
  9. 9.
    Franzini-Armstrong, C., 1970, Studies of the triad. I. Structure of the junction in frog twitch fibers, J. Cell Biol. 47: 488–499.PubMedCrossRefGoogle Scholar
  10. 10.
    Endo, M., 1977, Calcium release from the sarcoplasmic reticulum, Physiol. Rev. 57: 71–108.PubMedGoogle Scholar
  11. 11.
    Fabiato, A., 1985, Simulated calcium current can both cause calcium loading in and trigger calcium release from the sarcoplasmic reticulum of a skinned canine cardiac cell, J. Gen. Physiol. 85: 291–320.PubMedCrossRefGoogle Scholar
  12. 12.
    Chandler, W. K., Rakowski, R. F., and Schneider, M. F., 1976, A nonlinear voltage-dependent charge movement in frog skeletal muscle, J. Physiol. (London) 254: 245–283.Google Scholar
  13. 13.
    Vergara, J., Tsien, R. Y., and Delay, M., 1985, Inositol 1,4,5-trisphosphate: A possible chemical link in excitation-contraction coupling in muscle, Proc. Natl. Acad. Sci. USA 82: 6352–6356.PubMedCrossRefGoogle Scholar
  14. 14.
    Volpe, P., Salviati, G., Di Virgilio, F., and Pozzan, T., 1985, Inositol 1,4,5-trisphosphate induces calcium release from sarcoplasmic reticulum of skeletal muscle, Nature (London) 316: 347–349.CrossRefGoogle Scholar
  15. 15.
    Hille, B., and Campbell, D. T., 1976, An improved vaseline gap voltage clamp for skeletal muscle fibers, J. Gen. Physiol. 67: 265–293.PubMedCrossRefGoogle Scholar
  16. 16.
    Vergara, J., Bezanilla, F., and Salzberg, B. M., 1978, Nile blue fluorescence signals from cut single muscle fibers under voltage or current clamp conditions, J. Gen. Physiol. 72: 775–800.PubMedCrossRefGoogle Scholar
  17. 17.
    Delay, M., Ribalet, B., and Vergara, J., 1986, Caffeine potentiation of calcium release in frog skeletal muscle fibers, J. Physiol. (London) 375: 535–559.Google Scholar
  18. 18.
    Armstrong, CM., Bezanilla, F., and Horowicz, P., 1972, Twitches in the presence of ethylene glycol bis(-aminoethylether)-N-tetracetic acid, Biochem. Biophys. Acta 261:605–608.Google Scholar
  19. 19.
    Miledi, R., Parker, I., and Schalow, G., 1977, Measurement of calcium transients in frog muscle by the use of arsenazo III, Proc. R. Soc. B. (London) 198: 201–210.CrossRefGoogle Scholar
  20. 20.
    Atwater, I., Rojas, E., and Vergara, J., 1974, Calcium influxes and tension development in perfused single barnacle muscle fibers under membrane potential control, J. Physiol. (London) 243: 523–555.Google Scholar
  21. 21.
    Keynes, R. D., Rojas, E., Taylor, R. E., and Vergara, J., 1973, Calcium and potassium systems of a giant barnacle muscle fiber under membrane potential control, J. Physiol. (London) 229: 409–455.Google Scholar
  22. 22.
    Vergara, J., and Verdugo, P., 1988, Calcium transients in voltage-clamped barnacle muscle fibers, Biophys. J. 53: 647a.CrossRefGoogle Scholar
  23. 23.
    Schneider, M. F., and Chandler, W. K., 1973, Voltage-dependent charge movement in skeletal muscle: A possible step in excitation-contraction coupling, Nature (London) 242: 244–246.CrossRefGoogle Scholar
  24. 24.
    Aimers, W., 1978, Gating currents and charge movements in excitable membranes, Rev. Physiol. Biochem. Pharmacol. 82: 96–190.CrossRefGoogle Scholar
  25. 25.
    Adrian, R. H., and Peres, A., 1979, Charge movement and membrane capacity in frog muscle, J. Physiol. (London) 289: 83–97.Google Scholar
  26. 26.
    Huang, C. I.-H., 1982, Pharmacological separation of charge movement components in frog skeletal muscle, J. Physiol. (London) 324: 375–387.Google Scholar
  27. 27.
    Hui, C. S., 1983, Pharmacological studies of charge movement in frog skeletal muscle, J. Physiol. (London). 337: 509–529.Google Scholar
  28. 28.
    Vergara, J., and Caputo, C., 1983, Effects of tetracaine on charge movements and calcium signals in frog skeletal muscle fibers, Proc. Natl. Acad. Sci. USA 80: 1477–1481.PubMedCrossRefGoogle Scholar
  29. 29.
    Brum, G., and Rios, E., 1987, Intramembrane charge movement in frog skeletal muscle fibers, Properties of charge 2, J. Physiol. (London) 387: 489–517.Google Scholar
  30. 30.
    Lamb, G. D., 1986, Components of charge movement in rabbit skeletal muscle: The effect of tetracaine and nifedipine, J. Physiol. (London) 376: 85–100.Google Scholar
  31. 31.
    Simon, B. J., and Schneider, M. F., 1987, A comparison of the kinetics of charge movement and activation of SR calcium release during excitation in frog skeletal muscle, Biophys. J. 51: 550a.Google Scholar
  32. 32.
    Vergara, J., and Tsien, R. Y., 1985, Inositol-triphosphate-induced contractures in frog skeletal muscle fibers, Biophys. J. 47:351a.Google Scholar
  33. 33.
    Vergara, J., Asotra, K., and Delay, M., 1987, A chemical link in excitation-contraction coupling in skeletal muscle, in: Cell Calcium and the Control of Membrane Transport (L. J. Mandel and D. C. Eaton, Eds.), pp. 133–151, Rockefeller Press, New York.Google Scholar
  34. 34.
    Vergara, J., and Asotra, K., 1987, The chemical transmission mechanism of excitation-contraction coupling in skeletal muscle, News Physiol. Sci. 2: 182–186.Google Scholar
  35. 35.
    Berridge, M. J., and Irvine, R. F., 1984, Inositol triphosphate, a novel second messenger in cellular signal transduction, Nature (London) 312: 315–321.CrossRefGoogle Scholar
  36. 36.
    Katz, B., 1969, The Release of Neural Transmitter Substances (C. C. Thomas, Ed.), pp. 1–60, Charles C. Thomas, Springfield, Illinois.Google Scholar
  37. 37.
    Katz, B., and Miledi, R., 1965, The measurement of synaptic delay, and the time course of acetylcholine release at the neuromuscular junction, Proc. R. Soc. B. 161: 483–495.CrossRefGoogle Scholar
  38. 38.
    Katz, B., and Miledi, R., 1965, The effect of temperature on the synaptic delay at the neuromuscular junction, J. Physiol. (London) 181: 656–670.Google Scholar
  39. 39.
    Vergara, J., and Delay, M., 1986, A transmission delay and the effect of temperature at the triadic junction of skeletal muscle, Proc. R. Soc. Lond. Ser. B. 229: 97–110.CrossRefGoogle Scholar
  40. 40.
    Vergara, J., and Delay, M., 1985, The use of metallochromic Ca indicators in skeletal muscle, Cell Calcium 6: 119–132.PubMedCrossRefGoogle Scholar
  41. 41.
    Fuortes, M. G. F., and Hodgkin, A. L., 1964, Changes in time scale and sensitivity in the ommatidia of Limulus, J. Physiol. (London) 172: 239–263.Google Scholar
  42. 42.
    Baylor, D. A., Hodgkin, A. L., and Lamb, T. D., 1974, The electrical response of turtle cones to flashes and steps of light, J. Physiol. (London) 242: 685–727.Google Scholar
  43. 43.
    Fein, A., Payne, R., Corson, D. W., Berridge, M. J., and Irvine, R. F., 1984, Photoreceptor excitation and adaptation by inositol 1,4,5-trisphosphate, Nature 311: 157–160.PubMedCrossRefGoogle Scholar
  44. 44.
    Brown, J. E., Rubin, I. J., Ghalayani, A. J., Tarver, A. P., Irvine, R. F., Berridge, M. J., and Anderson, R. E., 1984, Myo-inositol polyphosphate may be a messenger for visual excitation in Limulus photoreceptor, Nature 311: 160–163.PubMedCrossRefGoogle Scholar
  45. 45.
    Yau, K-W., and Nakatani, K., 1985, Light-induced reduction of cytoplasmic tree calcium in retinal rod outer segment, Nature 313: 579–582.PubMedCrossRefGoogle Scholar
  46. 46.
    Hollingworth, S., and Marshall, M. W., 1981, A comparative study of charge movements in rat and frog skeletal muscle fibers, J. Physiol. (London) 321: 583–602.Google Scholar
  47. 47.
    Simon, B. J., and Beam, K. G., 1985, The influence of transverse tubular delays on the kinetics of charge movement in mammalian skeletal muscle, J. Gen. Physiol. 85: 21–42.PubMedCrossRefGoogle Scholar
  48. 48.
    Hidalgo, C., Carrasco, M. A., Magendzo, K., and Jaimovich, E., 1986, Phosphorylation of phosphatidylinositol by transverse tubule vesicles and its possible role in excitation-contraction coupling, FEBS Lett. 202: 69–73.PubMedCrossRefGoogle Scholar
  49. 49.
    Varsanyi, M., Messer, M., Brandt, N., and Heilmeyer, L. M. G., 1986, Phosphatidylinositol 4,5-bisphosphate formation in rabbit skeletal and heart muscle membranes, Biochem. Biophys. Res. Comm. 138: 1395–1404.PubMedCrossRefGoogle Scholar
  50. 50.
    Lagos, N., and Vergara, J., 1989, Phosphoinositide kinase and phospholipase-C activities in T-tubule membrane vesicles of frog skeletal muscle, Biophys. Soc. Abstracts 55: 236a.Google Scholar
  51. 51.
    Asotra, K., and Vergara, J., 1986, Levels of inositol phosphates in stimulated and relaxed muscles, Biophys. J. 49: 190a.Google Scholar
  52. 52.
    Hidalgo, C., Parra, C., Riquelme, G., Jaimovich, E., 1986, Transverse tubules from frog skeletal muscle: Purification and properties of vesicles sealed with the inside-out orientation, Biochim. Biophys. Acta 855: 79–88.PubMedCrossRefGoogle Scholar
  53. 53.
    Kirley, T. L., 1988, Purification and characterization of the Mg2+-ATPase from rabbit skeletal muscle transverse tubule, J. Biol. Chem. 263: 12682–12689.PubMedGoogle Scholar
  54. 54.
    Hess, H. H., and Derr, J. F., 1975, Assay of inorganic and organic phosphorus in the 0.1–5 nanomole range, Anal. Biochem. 63: 607–613.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1990

Authors and Affiliations

  • Julio Vergara
    • 1
  • Nestor Lagos
    • 1
  • Deida Compagnon
    • 1
  1. 1.Department of PhysiologyUniversity of California-Los AngelesLos AngelesUSA

Personalised recommendations