Regulation of the Ca2+ Sensitivity of Vascular Smooth Muscle Contractile Elements

  • Junji Nishimura
  • Cornelis van Breemen
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 308)


Ca2+ is assumed to be the primary regulator of vascular smooth muscle contractility (1). In addition, receptor stimulation may modulate the Ca2+ sensitivity of vascular smooth muscle myofilaments, probably due to activation of protein kinase C (PKC). Morgan and Morgan (2,3) were the first to measure tension simultaneously with intracellular Cat2+ concentration ([Ca2+]i) in strips of ferret portal vein, using the photoprotein aequorin. They found that α-adrenergic activation induced a peak of light emission during the period of force development which fell close to the basal value during force maintenance. It has also been reported that phorbol esters which activate PKC (4), induce contraction in intact vascular smooth muscle (5-9), and shift the pCa-tension curve to the left in permeabilized smooth muscle (10,11). Although these reports tend to support a role for PKC in enhancing Cat2+ sensitivity of vascular smooth muscle myofilaments, they fail to establish a clear link between receptors, G proteins, PKC and the myofilaments.


Smooth Muscle Sarcoplasmic Reticulum Sodium Nitroprusside Myosin Light Chain Kinase Contractile Element 
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.
    Somlyo AP. Excitation-contraction coupling and the ultrastructure of smooth muscle. Circ Res 57: 497, 1985.PubMedGoogle Scholar
  2. 2.
    Morgan JP, Morgan KG. Vascular smooth muscle: The first recorded Cat+ transients. Pflugers Arch 395: 75, 1982.PubMedCrossRefGoogle Scholar
  3. 3.
    Morgan JP, Morgan KG. Stimulus-specific patterns of intracellular calcium levels in smooth muscle of the ferret portal vein. J Physiol (Lond) 351: 155, 1984.Google Scholar
  4. 4.
    Nishizuka Y. Studies and perspectives of protein kinase C. Science 233: 305, 1986.PubMedCrossRefGoogle Scholar
  5. 5.
    Baraban JM, Gould RJ, Peroutka SJ, Snyder SH. Phorbol ester effects on neurotransmission: Interaction with neurotransmitters and calcium in smooth muscle. Proc Natl Acad Sci USA, 82: 604, 1985.PubMedCrossRefGoogle Scholar
  6. 6.
    Danthuluri NR, Deth RC. Phorbol ester-induced contraction of arterial smooth muscle and inhibition of a-adrenergic response. Biochem Biophys Res Comm 125: 1103, 1984.PubMedCrossRefGoogle Scholar
  7. 7.
    Forder J, Scriabine A, Rasmussen H. Plasma membrane calcium flux, protein kinase C activation and smooth muscle contraction. J Pharmacol Exp Ther 235: 267, 1985.PubMedGoogle Scholar
  8. 8.
    Rasmussen M, Forder J, Kojima I, Scriabine A. TPA-induced contraction of isolated rabbit vascular smooth muscle. Biochem Biophys Res Comm 122: 776, 1984.PubMedCrossRefGoogle Scholar
  9. 9.
    Khalil RA, van Breemen C. Sustained contraction of vascular smooth muscle: Calcium influx or C-kinase activation ? J Pharmacol Exp Ther 244: 537, 1988.PubMedGoogle Scholar
  10. 10.
    Itoh T, Kubota Y, Kuriyama H. Effects of phorbol ester on acetylcholine-induced Cat+ mobilization and contraction in the porcine coronary artery. J Physiol (Lond) 397: 401–419, 1988.Google Scholar
  11. 11.
    Nishimura J, van Breemen C. Direct regulation of smooth muscle contractile elements by second messengers. Biochem Biophys Res Comm 163: 929, 1989.PubMedCrossRefGoogle Scholar
  12. 12.
    Adelstein RS, Conti MA, Hathaway DR, Klee CB. Phosphorylation of smooth muscle myosin light chain kinase by the catalytic subunit of adenosine 3’:5’-monophosphate-dependent protein kinase. J Biol Chem 253: 8347, 1978.PubMedGoogle Scholar
  13. 13.
    Kamm KE, Stull JT. The function of myosin and myosin light chain kinase phosphorylation in smooth muscle. Annu Rev Pharmacol Toxicol 25: 593, 1985.PubMedCrossRefGoogle Scholar
  14. 14.
    Kamm KE, Stull JT. Regulation of smooth muscle contractile elements by second messengers. Annu Rev Physiol 51: 299: 313, 1989.Google Scholar
  15. 15.
    Itoh T, Kanmura Y, Kuriyama H, Sasaguri T. Nitroglycerine-and isoprenaline-induced vasodilation: assessment from the actions of cyclic nucleotides. Br J Pharmacol 84: 393, 1985.PubMedGoogle Scholar
  16. 16.
    Nishimura J, Kolber M, van Breemen C. Norepinephrine and GTPy-S increase myofilament Ca2+ sensitivity in a-toxin permeabilized arterial smooth muscle. Biochem Biophys Res Comm 157: 677, 1988.PubMedCrossRefGoogle Scholar
  17. 17.
    Nishimura J, van Breemen C. Possible involvement of actomyosin ADP complex in regulation of Ca2+ sensitivity in a-toxin permeabilized smooth muscle. Biochem Biophys Res Comm 165: 408, 1989.PubMedCrossRefGoogle Scholar
  18. 18.
    Fujiwara T, Itoh T, Kubota Y, Kuriyama H. Effect of guanosine nucleotides on skinned smooth muscle tissue of the rabbit mesenteric artery. J Physiol (Lond) 408: 535, 1989.Google Scholar
  19. 19.
    Schultz KD, Schultz K, Schultz J. Sodium nitroprusside and other smooth muscle-relaxants increase cyclic GMP levels in rat ductus deferens. Nature 265: 750, 1977.PubMedCrossRefGoogle Scholar
  20. 20.
    Cassidy P, Hoar PE, Kerrick WGL. Irreversible thiophosphorylation and activation of tension in functionally skipped rabbit ileum strips by [35S]ATP- S. J Biol Chem 254: 1 1148, 1979.Google Scholar
  21. 21.
    Hohman M. Aggregation of IgE receptors induces degranulation in rat basophilic leukemia cells permeabilized with a-toxin from Staphylococcus aureus. Proc Natl Acad Sci USA 85: 1624, 1988.PubMedCrossRefGoogle Scholar
  22. 22.
    Kitazawa T, Kobayashi S, Horiuchi K, Somlyo AV, Somlyo AP. Receptor coupled, permeabilized smooth muscle: role of the phosphatidylinositol cascade, G-proteins and modulation of the contractile response to Ca2+. JBiol Chem 264: 5339, 1989.Google Scholar
  23. 23.
    Morgan JP, Morgan KG. Alteration of cytoplasmic ionized calcium level in smooth muscle by vasodilators in the ferret. J Physiol (Lond) 357: 539, 1984.Google Scholar
  24. 24.
    Takuwa Y, Takuwa N, Rasumussen H. The effects of isoproterenol on intracellular calcium concentration. J Biol Chem 263: 762, 1988.PubMedGoogle Scholar
  25. 25.
    Takuwa Y and Rasmussen H. Measurement of cytoplasmic free Ca2+ concentration in rabbit aorta using the photoprotein, aequorin. J Clin Invest 80: 248, 1987.PubMedCrossRefGoogle Scholar
  26. 26.
    Waldman SA, Rapoport RM, Murad F. Atrial natriuretic factor selectively activates particular guanylate cyclase and elevates cyclic GMP in rat tissues. J Biol Chem 259: 14332, 1984.PubMedGoogle Scholar
  27. 27.
    Felbel J, Trockur B, Ecker T, Landgraf W, Hofmann F. Regulation of cytosolic calcium by cAMP and cGMP in freshly isolated smooth muscle cells from bovine trachea. J Biol Chem 263: 16764, 1988.PubMedGoogle Scholar
  28. 28.
    Kobayashi S, Kanaide H, Nakamura M. Cytosolic free calcium transient in cultured smooth muscle cells: Microfluorometric measurements. Science 229: 553, 1985.PubMedCrossRefGoogle Scholar
  29. 29.
    Karaki H, Sato K, Ozaki H, Murakami K. Effects of sodium nitroprusside on cytosolic calcium level in vascular smooth muscle. Eur J Pharmacol 156: 259, 1988.PubMedCrossRefGoogle Scholar
  30. 30.
    Kai H, Kanaide H, Matsumoto T, Nakamura M. 8-Bromoguanosine 3’:5’-cyclic monophosphate decreases intracellular free calcium concentrations in cultured vascular smooth muscle cells from rat aorta, FEBS Lett 221: 284, 1987.PubMedCrossRefGoogle Scholar
  31. 31.
    Jiang MJ, Morgan KG. Intracellular calcium levels in phorbol ester-induced contraction of vascular muscle. Am J Physiol 253: H1365, 1987.PubMedGoogle Scholar
  32. 32.
    Rembold CM, Murphy RA. Myoplasmic Ca2+ determines myosin phosphorylation in agonist-stimulated swine arterial smooth muscle. Circ Res 63: 593, 1988.PubMedGoogle Scholar
  33. 33.
    Kerrick WGL, Hoar PE. Inhibition of smooth muscle tension by cyclic AMP-dependent protein kinase. Nature (Lond) 292: 253, 1981.CrossRefGoogle Scholar
  34. 34.
    Cassidy PS, Kerrick WGL, Hoar PE, Malencik DA. Exogenous calmodulin increases Ca2+ sensitivity of isometric tension activation and myosin phosphorylation in skinned smooth muscle. Pflügers Arch 392: 115, 1981.PubMedCrossRefGoogle Scholar
  35. 35.
    Ruegg JC, Paul RJ. Vascular smooth muscle calmodulin and cyclic AMP-dependent protein kinase alter calcium sensitivity in porcine carotid skinned fibers. Circ Res 50: 394, 1982.PubMedGoogle Scholar
  36. 36.
    Saida K, van Breemen C. Cyclic AMP modulation of adrenoceptor mediated arterial smooth muscle contraction. J Gen Physiol 84: 307, 1984.PubMedCrossRefGoogle Scholar
  37. 37.
    Nishimura J, Khalil RA, van Breemen C. Evidence for increased myofilament Cat+ sensitivity in norepinephrine-activated vascular smooth muscle. Am J Physiol,in press.Google Scholar
  38. 38.
    Eisenberg E, Greene LE. The relation of muscle biochemistry to muscle physiology. Annu Rev Physiol 42: 293, 1980.PubMedCrossRefGoogle Scholar
  39. 39.
    Sleep JA, Hutton RL. Exchange between inorganic phosphate and adenosine 5’-triphosphate in the medium by actomyosin subfragment 1. Biochemistry 19: 1276, 1980.PubMedCrossRefGoogle Scholar
  40. 40.
    Sellers JR. mechanism of the phosphorylation-dependent regulation of smooth muscle heavy meromyosin. J Biol Chem 260: 15815, 1985.Google Scholar
  41. 41.
    Ventura-Clapier R, Mekhfi H, Vassort G. Role of creatine kinase in force development in chemically skinned rat cardiac muscle. J Gen Physiol 89: 815, 1987.PubMedCrossRefGoogle Scholar
  42. 42.
    Hoar PE, Mahoney CW, Kerrick WGL. MgADP-increases maximum tension and Cat+ sensitivity in skinned rabbit soleus fibers. Pflugers Arch 410: 30–36, 1987.PubMedCrossRefGoogle Scholar
  43. 43.
    Kerrick WGL, Hoar PE. Non-Ca2+-activated contraction in smooth muscle, in: Regulation and Contraction of Smooth Muscle, M.J. Siegmanm A.P. Somlyo, and N.L. Stephens, eds., A.R. Liss, New York, 1987.Google Scholar
  44. 44.
    Krisanda JM, Paul RJ. Phosphagen and metabolite content during contraction in porcine carotid artery. Am J Physiol 244: C385, 1983.PubMedGoogle Scholar
  45. 45.
    Gabella G. The force generated by a visceral smooth muscle. J Physiol (Lond) 263: 199, 1976.Google Scholar
  46. 46.
    Kushmerick MJ, Dillon PF, Meyer RA, Brown TR, Krisanda JM, Sweeney HE. 31P NMR spectroscopy, chemical analysis, and free Mg2+ of rabbit bladder and uterine smooth muscle. J Biol Chem 261: 14420, 1986.PubMedGoogle Scholar
  47. 47.
    Yoshizaki K, Radda GK, Inubushi T, Chance B. 1H- and 31P-NMR studies on smooth muscle of bullfrog stomach. Biochim Biophys Acta 928: 36, 1987.PubMedCrossRefGoogle Scholar
  48. 48.
    DeFeo TT, Morgan KG. Calcium-force relationships as detected with aequorin in two different vascular smooth muscles of the ferret. J Physiol (Lond) 369: 269, 1985.Google Scholar
  49. 49.
    Lash JA, Sellers JR, Hathaway DR. The effects of caldesmon on smooth muscle heavy actomeromyosin ATPase activity and binding of heavy meromyosin to actin. J Biol Chem 261: 16155, 1986.PubMedGoogle Scholar
  50. 50.
    Sobue K, Muramoto Y, Fujita M, Kakiuchi S. Purification of a calmodulin-binding protein from chicken gizzard that interacts with F-actin. Proc Natl Acad Sci USA 78: 5652, 1981.PubMedCrossRefGoogle Scholar
  51. 51.
    Ikebe M, Reardon S. Binding of caldesmon to smooth muscle myosin. J Biol Chem 263: 3055, 1988.PubMedGoogle Scholar
  52. 52.
    Sutherland C, Walsh MP. Phosphorylation of caldesmon prevents its interaction with smooth muscle myosin. J Biol Chem 264: 578, 1989.PubMedGoogle Scholar
  53. 53.
    Marston SB. Aorta caldesmon inhibits actin activation of thiophosphorylated heavy meromyosin Mgt+-ATPase activity by slowing the rate of product release. FEBS Lett 238: 147, 1988.PubMedCrossRefGoogle Scholar
  54. 54.
    Marston SB. What is the latch? New ideas about tonic contraction in smooth muscle. J Musc Res Cell Motility 10: 97, 1989.CrossRefGoogle Scholar
  55. 55.
    Dantzig JA, Goldman YE. Suppression of muscle contraction by vanadate: Mechanical and ligand binding studies on glycerol-extracted rabbit fibers. J Gen Physiol 86: 305, 1985.PubMedCrossRefGoogle Scholar
  56. 56.
    Umekawa H, Hidaka H. Phosphorylation of caldesmon by protein kinase C. Biochem Biophys Res Comm 132: 56, 1985.PubMedCrossRefGoogle Scholar
  57. 57.
    Park S, Rasmussen H. Carbachol-induced protein phosphorylation changes in bovine tracheal smooth muscle. J Biol Chem 261: 15734, 1986.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Junji Nishimura
    • 1
  • Cornelis van Breemen
    • 1
  1. 1.Department of Pharmacology University of Miami, School of MedicineMiamiUSA

Personalised recommendations