Advertisement

Cell Biochemistry and Biophysics

, Volume 46, Issue 3, pp 233–251 | Cite as

Theoretical and experimental investigation of calcium-contraction coupling in airway smooth muscle

  • Prisca Mbikou
  • Ales Fajmut
  • Milan Brumen
  • Etienne Roux
Original Article

Abstract

We investigated theoretically and experimentally the Ca2+-contraction coupling in rat tracheal smooth muscle. [Ca2+]i, isometric contraction and myosin light chain (MLC) phosphorylation were measured in response to 1 mM carbachol. Theoretical modeling consisted in coupling a model of Ca2+-dependent MLC kinase (MLCK) activation with a four-state model of smooth muscle contractile apparatus. Stimulation resulted in a short-time contraction obtained within 1 min, followed by a long-time contraction up to the maximal force obtained in 30 min. ML-7 and Wortmannin (MLCK inhibitors) abolished the contraction. Chelerythrine (PKC inhibitor) did not change the short-time, but reduced the long-time contraction. [Ca2+ i responses of isolated myocytes recorded during the first 90 s consisted in a fast peak, followed by a plateau phase and, in 28% of the cells, superimposed Ca2+ oscillations. MLC phosphorylation was maximal at 5 s and then decreased whereas isometric contraction followed a Hill-shaped curve. The model properly predicts the time course of MLC phosphorylation and force of the short-time response. With oscillating Ca2+ signal, the predicted force does not oscillate. According to the model, the amplitude of the plateau and the frequency of oscillations encode for the amplitude of force, whereas the peak encodes for force velocity. The long-time phase of the contraction, associated with a second increase in MLC phosphorylation, may be explained, at least partially, by MLC phosphatase (MLCP) inhibition, possibly via PKC inhibition.

Index Entries

Tracheal cell Rat Mathematical model Myosin light chain kinase Myosin light chain Myosin light chain phosphatase Cross bridge cycling contraction Calcium 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Ay, B., Prakash, Y. S., Pabelick, C. M., and Sieck, G. C. (2004) Store-operated Ca2+ entry in porcine airway smooth muscle. Am. J. Physiol. Lung Cell Mol. Physiol. 286, L909-L917.PubMedCrossRefGoogle Scholar
  2. 2.
    Hyvelin, J. M., Martin, C., Roux, E., Marthan, R. and Savineau, J. P. (2000) Human isolated bronchial smooth muscle contains functional ryanodine/caffeine-sensitive Ca-release channels. Am. J. Resp. Crit. Care Med. 162, 687–694.PubMedGoogle Scholar
  3. 3.
    Kannan, M. S., Prakash, Y. S., Brenner, T., Mickelson, J. R. and Sieck, G. C. (1997) Role of ryanodine receptor channels in Ca2+ oscillations of porcine tracheal smooth muscle. Am. J. Physiol. 272, L659-L664.PubMedGoogle Scholar
  4. 4.
    Liu, X. and Farley, J. M. (1996) Frequency modulation of acetylcholine-induced Ca(++)-dependent Cl-current oscillations are mediated by 1, 4, 5-trisphosphate in tracheal myocytes. J. Pharmacol. Exp. Ther. 277, 796–804.PubMedGoogle Scholar
  5. 5.
    Kajita, J. and Yamaguchi, H. (1993) Calcium mobilization by muscarinic cholinergic stimulation in bovine single airway smooth muscle. Am. J. Physiol. 264, L496-L503.PubMedGoogle Scholar
  6. 6.
    Nuttle, L. C. and Farley, J. M. (1996) Frequency modulation of acetylcholine-induced oscillations in Ca++ and Ca(++)-activated Cl-current by cAMP in tracheal smooth muscle. J. Pharmacol. Exp. Ther. 277, 753–760.PubMedGoogle Scholar
  7. 7.
    Prakash, Y. S., Pabelick, C. M., Kannan, M. S., and Sieck, G. C. (2000) Spatial and temporal aspects of ACh-induced [Ca2+]i oscillations in porcine tracheal smooth muscle. Cell Calcium 27, 153–162.PubMedCrossRefGoogle Scholar
  8. 8.
    Prakash, Y. S., Kannan, M. S., and Sieck, G. C. (1997) Regulation of intracellular calcium oscillations in porcine tracheal smooth muscle cells. Am. J. Physiol. 272, C966-C975.PubMedGoogle Scholar
  9. 9.
    Roux, E., Guibert, C., Savineau, J. P., and Marthan, R. (1997) [Ca2+ i oscillations induced by muscarinic stimulation in airway smooth muscle cells: receptor subtypes and correlation with the mechanical activity. Br. J. Pharmacol. 120, 1294–1301.PubMedCrossRefGoogle Scholar
  10. 10.
    Roux, E., Duvert, M. and Marthan, R. (2002) Combined effect of chronic hypoxia and in vitro exposure to gas pollutants on airway reactivity. Am. J. Physiol. Lung Cell Mol. Physiol. 283, L628-L635.PubMedGoogle Scholar
  11. 11.
    Sims, S. M., Jiao, Y., and Zheng, Z. C. (1996) Intracellular calcium stores in isolated tracheal smooth muscle cells. Am. J. Physiol. 271, L300-L309.PubMedGoogle Scholar
  12. 12.
    Bergner, A. and Sanderson, M. J. (2002) Acetylcholine-induced calcium signaling and contraction of airway smooth muscle cells in lung slices. J. Gen. Physiol. 119, 187–198.PubMedCrossRefGoogle Scholar
  13. 13.
    Hyvelin, J. M., Roux, E., Prevost, M. C., Savineau, J. P. and Marthan, R. (2000) Cellular mechanisms of acrolein-induced alteration in calcium signaling in airway smooth muscle. Toxicol. Appl. Pharmacol. 164, 176–183.PubMedCrossRefGoogle Scholar
  14. 14.
    Bergner, A. and Sanderson, M. J. (2002) ATP stimulates Ca2+ oscillations and contraction in airway smooth muscle cells of mouse lung slices. Am. J. Physiol. Lung Cell Mol. Physiol. 283, L1271-L1279.PubMedGoogle Scholar
  15. 15.
    Roux, E. and Marhl, M. (2004) Role of sarcoplasmic reticulum and mitochondria in Ca2+ removal in airway myocytes. Biophys. J. 86, 2583–2595.PubMedGoogle Scholar
  16. 16.
    Mounkaila, B., Marthan, R., and Roux, E. (2005) Biphasic effect of extracellular ATP on human and rat airways is due to multiple P2 purinoceptor activation. Resp. Res. 6, 143.CrossRefGoogle Scholar
  17. 17.
    Roux, E., Hyvelin, J. M., Savineau, J. P., and Marthan, R. (1998) Calcium signaling in airway smooth muscle cells is altered by in vitro exposure to the aldehyde acrolein. Am. J. Resp. Cell Mol. Biol. 19, 437–444.Google Scholar
  18. 18.
    Perez, J. F. and Sanderson, M. J. (2005) The frequency of calcium oscillations induced by 5-HT, ACH, and KCl determine the contraction of smooth muscle cells of intrapulmonary bronchioles. J. Gen. Physiol. 125, 535–553.PubMedCrossRefGoogle Scholar
  19. 19.
    Somlyo, A. P. and Somlyo, A. V. (2003) Ca2+ sensitivity of smooth muscle and nonmuscle myosin II: Modulated by G proteins, kinases, and myosin phosphatase. Physiol. Rev. 83, 1325–1358.PubMedGoogle Scholar
  20. 20.
    Somlyo, A. P. and Somlyo, A. V. (1994) Signal transduction and regulation in smooth muscle. Nature 372, 231–236.PubMedCrossRefGoogle Scholar
  21. 21.
    Hirano, K., Derkach, D. N., Hirano, M., Nishimura, J., and Kanaide, H. (2003) Protein kinase network in the regulation of phosphorylation and dephosphorylation of smooth muscle myosin light chain. Mol. Cell Biochem. 248, 105–114.PubMedCrossRefGoogle Scholar
  22. 22.
    Smith, P. G., Roy, C., Dreger, J., and Brozovich, F. (1999) Mechanical strain increases velocity and extent of shortening in cultured airway smooth muscle cells. Am. J. Physiol. Lung Cell Mol. Physiol. 277, L343-L348.Google Scholar
  23. 23.
    Ma, X., Cheng, Z., Kong, H., Wang, Y., Unruh, H., Stephens, N. L., and Laviolette, M. (2002) Changes in biophysical and biochemical properties of single bronchial smooth muscle cells from asthmatic subjects. Am. J. Physiol. Lung Cell Mol. Physiol. 283, L1181-L1189.PubMedGoogle Scholar
  24. 24.
    Fredberg, J. J. (2002) Airway narrowing in asthma: does speed kill? Am. J. Physiol. Lung Cell Mol. Physiol. 283, L1179-L1180.PubMedGoogle Scholar
  25. 25.
    Hai, C. M. and Murphy, R. A. (1988) Cross-bridge phosphorylation and regulation of latch state in smooth muscle. Am. J. Physiol. Cell Physiol. 254, C99-C106.Google Scholar
  26. 26.
    Rembold, C. M. and Murphy, R. A. (1990) Latch-bridge model in smooth-muscle-[Ca-2+]i can quantitatively predict stress. Am. J. Physiol. 259, C251-C257.PubMedGoogle Scholar
  27. 27.
    Yu, S. N., Crago, P. E., and Chiel, H. J. (1997) A nonisometric kinetic model for smooth muscle. Am. J. Physiol. Cell Physiol. 272, C1025-C1039.Google Scholar
  28. 28.
    Fredberg, J. J., Inoyue, D. S., Mijalovich, S. M., and Butler, J. P. (1999) Perturbed equilbrium of myosin binding in airway smooth muscle and its implications in bronchospasm. Am. J. Resp. Crit. Care Med. 159, 959–967.PubMedGoogle Scholar
  29. 29.
    Rembold, C. M., Wardle, R. L., Wingard, C. J., Batts, T. W., Etter, E. F., and Murphy, R. A. (2004) Cooperative attachment of cross bridges predicts regulation of smooth muscle force by myosin phosphorylation. Am. J. Physiol. Cell Physiol. 287, C594-C602.PubMedCrossRefGoogle Scholar
  30. 30.
    Fajmut, A., Brumen, M., and Schuster, S. (2005) Theoretical model of the interactions between Ca2+, calmodulin and myosin light chain kinase. FEBS Lett. 579, 4361–4366.PubMedCrossRefGoogle Scholar
  31. 31.
    Fajmut, A., Dobovisek, A., and Brumen, M. (2005) Mathematical modeling of the relation between myosin phosphorylation and stress development in smooth muscles. J. Chem. Inf. Model 45, 1610–1615.PubMedCrossRefGoogle Scholar
  32. 32.
    Kato, S., Osa, T., and Ogasawara, T. (1984) Kinetic model for isometric contraction in smooth muscle on the basis of myosin phosphorylation hypothesis. Biophys. J. 46, 35–44.PubMedGoogle Scholar
  33. 33.
    Lukas, T. J. (2004) A signal transduction pathway model prototype I: from agonist to cellular endpoint. Biophys. J. 87, 1406–1416.PubMedCrossRefGoogle Scholar
  34. 34.
    Fajmut, A., Jagodic, M., and Brumen, M. (2005) Mathematical modeling of the myosin light chain kinase activation. J. Chem. Inf. Model. 45, 1605–1609.PubMedCrossRefGoogle Scholar
  35. 35.
    Roux, E. and Marhl, M. (2004) Role of sarcoplasmic reticulum and mitochondria in ca(2+) removal in airway myocytes. Biophys. J. 86, 2583–2595.PubMedCrossRefGoogle Scholar
  36. 36.
    Teoh, H., Zacour, M., Wener, A. D., Gunaratnam, L., and Ward, M. E. (2003) Increased myofibrillar protein phosphatase-1 activity impairs rat aortic smooth muscle activation after hypoxia. Am. J. Physiol. Heart Circ. Physiol. 284, H1182-H1189.PubMedGoogle Scholar
  37. 37.
    Shojo, H. and Kaneko, Y. (2001) Oxytocin-induced phosphorylation of myosin light chain is mediated by extracellular calcium influx in pregnant rat myometrium. J. Mol. Recognit. 14, 401–405.PubMedCrossRefGoogle Scholar
  38. 38.
    Satpathy, M., Gallagher, P., Lizotte-Waniewski, M., and Srinivas, S. P. (2004) Thrombin-induced phosphorylation of the regulatory light chain of myosin II in cultured bovine corneal endothelial cells. Exp. Eye Res. 79, 477–486.PubMedCrossRefGoogle Scholar
  39. 39.
    Geguchadze, R., Zhi, G., Lau, K. S., Isotani, E., Persechini, A., Kamm, K. E., and Stull, J. T. (2004) Quantitative measurements of Ca2+/calmodulin binding and activation of myosin light chain kinase in cells. FEBS Lett. 557, 121–124.PubMedCrossRefGoogle Scholar
  40. 40.
    Van Lierop, J. E., Wilson, D. P., Davis, J. P., Tikunova, S., Sutherland, C., Walsh, M. P., and Johnson, J. D. (2002) Activation of smooth muscle myosin light chain kinase by calmodulin. Role of LYS30 and GLY40. J. Biol. Chem. 277, 6550–6558.PubMedCrossRefGoogle Scholar
  41. 41.
    Button, L., Mireylees, S. E., Germack, R., and Dickenson, J. M. (2005) Phosphatidylinositol 3-kinase and ERK1/2 are not involved in adenosine A1, A2A or A3 receptor-mediated preconditioning in rat ventricle strips. Exp. Physiol. 90, 747–754.PubMedCrossRefGoogle Scholar
  42. 42.
    Burdyga, T., Mitchell, R. W., Ragozzino, J., and Ford, L. E. (2003) Force and myosin light chain phosphorylation in dog airway smooth muscle activated in different ways. Resp. Physiol. Neurobiol. 137, 141–149.CrossRefGoogle Scholar
  43. 43.
    Ansari, H. R., Kaddour-Djebbar, I., and Abdel-Latif, A. A. (2004) Effects of prostaglandin F2alpha, latanoprost and carbachol on phosphoinositide turnover, MAP kinases, myosin light chain phosphorylation and contraction and functional existence and expression of FP receptors in bovine iris sphincter. Exp. Eye Res. 78, 285–296.PubMedCrossRefGoogle Scholar
  44. 44.
    Hirano, K., Kanaide, H., and Nakamura, M. (1989) Effects of okadaic acid on cytosolic calcium concentrations and on contractions of the porcine coronary artery. Br. J. Pharmacol. 98, 1261–1266.PubMedGoogle Scholar
  45. 45.
    Naline, E., Candenas, M. L., Palette, C., Moreau, J., Norte, M., Martin, J. D., Pays, M., and Advenier, C. (1994) Effects of okadaic acid on the human isolated bronchus. Eur. J. Pharmacol. 256, 301–309.PubMedCrossRefGoogle Scholar
  46. 46.
    Neumann, J., Boknik, P., Herzig, S., Schmitz, W., Scholz, H., Gupta, R. C., and Watanabe, A. M. (1993) Evidence for physiological functions of protein phosphatases in the heart: evaluation with okadaic acid. Am. J. Physiol. 265, H257-H266.PubMedGoogle Scholar
  47. 47.
    Yang, K. X. and Black, J. L. (1995) The involvement of protein kinase C in the contraction of human airway smooth muscle. Eur. J. Pharmacol. 275, 283–289.PubMedCrossRefGoogle Scholar
  48. 48.
    Li, L., Eto, M., Lee, M. R., Morita, F., Yazawa, M., and Kitazawa, T. (1998) Possible involvement of the novel CPI-17 protein in protein kinase C signal transduction of rabbit arterial smooth muscle. J. Physiol. 508, 871–881.PubMedCrossRefGoogle Scholar
  49. 49.
    Woodsome, T. P., Eto, M., Everett, A., Brautigan, D. L., and Kitazawa, T. (2001) Expression of CPI-17 and myosin phosphatase correlates with Ca(2+) sensitivity of protein kinase C-induced contraction in rabbit smooth muscle. J. Physiol. 535, 553–564.PubMedCrossRefGoogle Scholar
  50. 50.
    Hai, C. M. and Szeto, B. (1992) Agonist-induced myosin phosphorylation during isometric contraction and unloaded shortening in airway smooth muscle. Am. J. Physiol. Lung Cell Mol. Physiol. 262, L53-L62.Google Scholar
  51. 51.
    Singer, H. A., Kamm, K. E., and Murphy, R. A. (1986) Estimates of activation in arterial smooth muscle. Am. J. Physiol. 251, C465–73.PubMedGoogle Scholar
  52. 52.
    Saitoh, M., Ishikawa, T., Matsushima, S., Naka, M., and Hidaka, H. (1987) Selective inhibition of catalytic activity of smooth muscle myosin light chain kinase. J. Biol Chem. 262, 7796–7801.PubMedGoogle Scholar
  53. 53.
    Bai, Y. and Sanderson, M. J. (2006) Modulation of the Ca2+ sensitivity of airway smooth muscle cells in murine lung slices. Am. J. Physiol. Lung Cell Mol. Physiol. 291(2), L208-L221.PubMedCrossRefGoogle Scholar
  54. 54.
    Hai, C.-M. and Kim, H. R. (2005) An expanded latchbridge model of protein kinase C-mediated smooth muscle contraction. J. Appl. Physiol. 98, 1356–1365.PubMedCrossRefGoogle Scholar
  55. 55.
    Sieck, G. C., Han, Y.-S., Pabelick, C. M., and Prakash, Y. S. (2001) Temporal aspects of excitation-contraction coupling in airway smooth muscle. J. Appl. Physiol. 91, 2266–2274.PubMedGoogle Scholar
  56. 56.
    Kasturi, R., Vasulka, C., and Johnson, J. (1993) Ca2+, caldesmon, and myosin light chain kinase exchange with calmodulin. J. Biol. Chem. 268, 7958–7964.PubMedGoogle Scholar
  57. 57.
    Török, K. and Trentham, D. R. (1994) Mechanism of 2-chloro-(epsilon-amino-Lys75)-[6-[4-(N,N-diethylamino)phenyl]-1,3,5-triazin-4-yl]calmodulin interactions with smooth muscle myosin light chain kinase and derived peptides. Biochemistry 33, 12807–12820.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc 2006

Authors and Affiliations

  • Prisca Mbikou
    • 1
  • Ales Fajmut
    • 3
  • Milan Brumen
    • 3
    • 4
  • Etienne Roux
    • 1
    • 2
  1. 1.Laboratoire de Physiologie Cellulaire RespiratoireUniversité Bordeaux 2BordeauxFrance
  2. 2.Inserm, E356BordeauxFrance
  3. 3.Department of Biophysics and Faculty of Education, Department of PhysicsUniversity of Maribor, Medical FacultyMariborSlovenia
  4. 4.Institute Jozef StefanLjubljanaSlovenia

Personalised recommendations