Skip to main content
SpringerLink
Log in

Calcium and smooth muscle contraction

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

The fact that smooth muscle exists in almost every hollow organ and is involved in a large number of disease states has led to a vast increase in smooth muscle research, covering areas from testing response to antagonists and agonists to measuring the molecular force generated by a single actin filament. Yet, the exact mechanisms regulating contractile response of smooth muscle remain unsolved. Calcium has been a central player in mediating smooth muscle contraction through binding with calmodulin, although there is evidence showing that under special circumstances smooth muscle can contract without change in intracellular Ca2+. In addition to the major regulatory pathway of Ca2+-calmodulin-mysoin light chain kinase, there are other thin filament linked regulatory mechanisms in which Ca2+-calmodulin dependent phosphorylation of calponin and caldesmon may be involved. Ca2+ sensitivity of smooth muscle contraction may vary under different situations and this has recently been recognized as an important regulatory mechanism. Examples are protein kinase C (PKC) dependent phosphorylation of myosin light chain kinase which results in partial inhibition of contraction, and activation of myosin light chain phosphatase. There is new evidence howing that not only does Ca2+ regulate contraction by regulating the interaction of contractile proteins in smooth muscle, but also that shortening of smooth muscle itself reduces intracellular Ca2+ concentration, via a negative feedback.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Filo RS, Bohr DF, Rügg JC: Glycerinated skeletal and smooth muscle: calcium and magnesium depdence. Science 147: 1581–1583, 1965

    Google Scholar 

  2. Bolton TB: Mechanisms of action of transmitters and other substances on smooth muscle. Physiol Rev 59: 606–718, 1979

    Google Scholar 

  3. Van Breemen C, Saida K: Cellular mechanisms regulating [Ca2+]i smooth muscle. Annu Rev Physiol 51: 315–329, 1989

    Google Scholar 

  4. Williams DA, Fay FS: Calcium transients and resting levels in isolated smooth muscle cells as monitored with quin-2. Am J Physiol 250: C779-C791, 1986

    Google Scholar 

  5. Hurwitz L: Pharmacology of calcium channels and smooth muscle. Annu Rev Pharmacol Toxicol 26: 225–258, 1986

    Google Scholar 

  6. Yamada K, Goto A, Matsuoka H, Sugimoto T: Alterations of calcium channels in vascular smooth muscle cells from spontaneously hypertensive rats. Jpn Heart J 33(5): 727–734, 1992

    Google Scholar 

  7. Chadwick CC, Saito A, Fleischer S: Isolation and characterization of the inositol trisphosphate receptor from smooth muscle. Proc Natl Acad Sci 87: 2132–2136, 1990

    Google Scholar 

  8. Janis RA, Silver PJ, Triggle DJ: Drug action and cellular calcium regulation. Adv Drug Res 16: 309–591, 1987

    Google Scholar 

  9. Casteels R, Wuytack F, Himpens B, Raeymaekers L: Regulatory systems for the cytoplasmic calcium concentration in smooth muscle. Biomed Biochim Acta 45: S147-S152, 1986

    Google Scholar 

  10. Fujimoto T: Calcium pump of the plasma membrane is localized in caveolae. J Cell Biol 120(5): 1147–1157, 1993

    Google Scholar 

  11. Sumida M, Okuda H, Hamada M: Ca2+, Mg2+-ATPase of microsomal membranes from bovine aortic smooth muscle. Identification and characterization of an acid-stable phosphorylated intermediate of the Ca2+, Mg2+-ATPase. J Biochem 96: 1365–1364, 1984

    Google Scholar 

  12. Raeymaekers L, Jones LR: Evidence for the presence of phosphlamban in the endoplasmic reticulum of smooth muscle. Biochim Biophys Acta 882: 258–265, 1986

    Google Scholar 

  13. Somlyo AP: Ultrastructure of vascular smooth muscle. In: D.F. Bohr, A.P. Somlyo and H.V. Sparks. The Handbook of Physiology, The cardiovascular system. Vol. 2. Vascular smooth muscle. Am Physiol Soc, Washington, 1980, pp 33–67

    Google Scholar 

  14. Stephens NL, Kong SK, Seow CY: Mechanisms of increased shortening of sensitized airway smooth muscle. In: C.L. Armour and J.L. Black (eds). Mechanisms in Asthma, Liss, New York, 1988, pp 231–254

    Google Scholar 

  15. Bagby RM, Young AM, Dotson RS, Fisher AB, McKinnon: Contraction of single smooth muscle cells frombufo marinus stomatch. Nature 234: 351–352, 1971

    Google Scholar 

  16. Gabella G: Structure of smooth muscle, In: E. Bulbring, A.F. Brading, A.W. Jones and T. Tomita, (eds). Smooth Muscle, An Assessment of Current Knowledge, Edward Arnold, London 1981, pp 1–46

    Google Scholar 

  17. Tan JL, Ravid S, Spudich JA: Control of non-muscle myosin by phosphorylation. Ann Rev Biochem 61: 721–759, 1992

    Google Scholar 

  18. Stephens NL, Seow CY, Halayko AJ, Jiang H: The biophysics and biochemistry of smooth muscle contraction. Can J Pharmacol Physiol 70: 515–531, 1992a

    Google Scholar 

  19. Malmqvist U, Arner A: Correlation between isoform composition of the 17 kDa myosin light chain and maximal shortening velocity in smooth muscle. Eur J Physiol 418: 523–530, 1991

    Google Scholar 

  20. Sobieszek A: Vertebrate smooth muscle myosin: enzymatic and structural properties. In: N.L. Stephens (ed.) Biochemistry of Smooth Muscle, Univ Park Press, Baltimore, 1977, pp 413–444.

    Google Scholar 

  21. Kamm KE, Stull JT: Regulation of smooth muscle contractile elements by second messengers. Annu Rev Physiol 51: 299–313, 1989

    Google Scholar 

  22. Miyata H, Chacko S: Role of tropomyosin is smooth muscle contraction: effect of tropomyosin binding to actin on actin-activation of myosin ATPase. Biochemistry 25: 2725–2729, 1986

    Google Scholar 

  23. 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 78: 5652–5655, 1981

    Google Scholar 

  24. Walsh MP: Smooth muscle caldesmon. In: N. Sperelakis and J.D. Wood (eds). Wiley-Liss, New York, 1990, pp 127–140

    Google Scholar 

  25. Ngai PK, Walsh MP: The effects of phosphorylation of smooth muscle caldesmon. Biochem J 244: 417–425, 1987

    Google Scholar 

  26. Tanaka T, Ohta H, Kanda K, Tanaka T, Hidaka H, Sobue K: Phosphorylation of high-Mr caldesmon by protein kinase C modulates the regulatory function of this protein on the interaction between actin and myosin. Eur J Biochem 188: 495–500, 1990

    Google Scholar 

  27. Kerrick WGL, Walsh MP, Sutherland, Hoar PE: Caldesmon is required for the activation of smooth muslce contraction in skinned gizzard cells. Biophys J 55: 70a, 1989

    Google Scholar 

  28. Walsh MP: Calcium-dependent mechanisms of regulation of smooth muscle contraction. Biochem Cell Biol 69: 771–800, 1991

    Google Scholar 

  29. Takahashi K, Hiwada K, Kokubu T: Isolation and characterization of a 34,000-dalton calmodulin- and F-actin-binding protein from chicken gizzard smooth muscle. Biochem Biophys Res Commun 141: 20–26, 1986

    Google Scholar 

  30. Winder SJ, Sutherland C, Walsh MP: Biochemical and functional characterization of smooth muscle calponin. In: R.S. Moreland (ed). Regulation of smooth muscle: Progress in Solving the Puzzle. Plenum Press, New York, 1991, pp 37–52

    Google Scholar 

  31. Cohen P: The structure and regulation of protein phosphatases. Annu Rev Biochem 58: 453–508, 1989

    Google Scholar 

  32. Schlender KK, Wang W, Wilson SE: Evidence for a latent form of protein phosphatase 1 associated with cardiac myofibrils. Biochem Biophys Res Commun 159: 72–78, 1989

    Google Scholar 

  33. Bialojan C, Rügg JC, Disalvo J: Phosphatase-mediated modulation of actin-myosin interaction in bovine aortic actomyosin and skinned porcine carotid artery. Proc Soc Exp Biol Med 178: 36–45, 1985

    Google Scholar 

  34. Haeberle JR, Hathaway DR, DePaoli-Roach AA: Dephosphorylation of myosin by the catalytic subunit of a type-2 phosphatase produces relaxation of chemically skinned uterine smooth muscle. J Biol Chem 260: 9965–9968, 1985

    Google Scholar 

  35. Ishihara H, Ozaki H, Sato K, Hori M, Karaki H, Watabe S, Kato Y, Rusetani N, Hashimoto K, Uemura D, Hartshorne DJ: Calcium-independent activation of contractile apparatus in smooth muscle b calyculin-A. J Pharmacol Exp Ther 250: 388–396, 1989

    Google Scholar 

  36. Berner PF, Somlyo AV, Somlyo AP: Hypertrophy-induced increase of intermediate filaments in vascular smooth muscle. J Cell Biol 88: 96–101, 1981

    Google Scholar 

  37. Rasmussen H, Takuwa Y, Park S: Protein kinase C in the regulation of smooth muscle contraction. FASEB J 1: 177–185, 1987

    Google Scholar 

  38. Fay FS, Fogarty K, Fugiwari K: The organization of the contractile apparatus in single isolated smooth muscle cells. In: N.L. Stephens, (ed). Smooth Muscle Contraction. Marcel Dekker, New York, 1984, p 75

    Google Scholar 

  39. Stull JT, Gallagher PJ, Herring BP, Kamm KE: Vascular smooth muscle contractile elements, cellular regulation. Hypertension 17: 723–732, 1991a

    Google Scholar 

  40. Tanaka T: Calmodulin-dependent calcium signal transduction. Jpn J Pharmacol 46: 101–107, 1988

    Google Scholar 

  41. Kitazawa T, Masuo M, Somloy AP: G protein-mediated inhibition of myosin light chain phosphatase in vascular smooth muscle. Proc Natl Acad Sci (USA) 88(20): 9307–9310, 1991

    Google Scholar 

  42. Kitazawa T, Masuo M, Somlyo AP: G protein-activation inhibits smooth muscle MLC phosphatase to increase the contractile sensitivity to Ca2+. Jpn J Pharmacol 58 suppl 2: 348p, 1992

  43. Dillon PF, Aksoy MO, Driska SP, Murphy RA: Myosin phosphorylation and the cross-bridge cycle in arterial smooth muscle. Science 211: 495–497, 1981

    Google Scholar 

  44. Aksoy MO, Murphy RA, Kamm KE: Role of Ca2+ and myosin light chain phosphorylation in regulation of smooth muscle. Am J Physiol 242: C109-C116, 1982

    Google Scholar 

  45. Chatterjee M, Murphy RA: Calcium-dependent stress maintenance without myosin phosphorylation in skinned smooth muscle. Science 221: 464–466, 1983

    Google Scholar 

  46. Rembold CM, Murphy RA: Latch-bridge model in smooth muscle: [Ca2+]i can quantitatively predict stress. Am J Physiol 259: C251-C257, 1990

    Google Scholar 

  47. Hai C-M, Murphy RA: Cross-bridge phosphorylation and regulation of latch state in smooth muscle. Am J Physiol 254: C99-C106, 1988

    Google Scholar 

  48. Siegman MJ, Butler TM, Mooers SU: Phosphatase inhibition with okadaic acid does not alter the relationship between force and myosin light chain phosphorylation in permeabilized smooth muscle. Biochem Biophys Res Commun 161: 838–842, 1989

    Google Scholar 

  49. Tansey MG, Hori M, Karaki H, Kamm KE, Stull JT: Okadaic acid uncouples myosin light chain phosphorylation and tension in smooth muscle. FEBS Lett 270: 219–221, 1990

    Google Scholar 

  50. Ashizawa N, Kobayashi F, Tanaka Y, Nakayama K: Relaxing action of okadaic acid, a black sponge toxin, on the arterial smooth muscle. Biochem Biophys Res Commun 162: 971–976, 1989

    Google Scholar 

  51. Oishi K, Takano-Ohmuro H, Minakawa-Matsuo N, Suga O, Karibe H, Kohama K, Uchida MK: Oxytocin contracts rat uterine smooth muscle in Ca2+-free medium without any phosphorylation of myosin light chain. Biochem Biophys Res Commun 176: 122–128, 1991

    Google Scholar 

  52. Gerthoffer WT: Dissociation of myosin phosphorylation and active tension during muscarinic stimulation of tracheal smooth muscle. J Pharmacol Exp Ther 240: 8–15, 1987

    Google Scholar 

  53. Winder SJ, Walsh MP: Smooth muscle calponin. Inhibition of actomyosin MgATPase and regulation by phosphorylation. J Biol Chem 265: 10148–10155, 1990

    Google Scholar 

  54. Pohl J, Walsh MP, Gerthoffer WT: Calponin and caldesmon phosphorylation in canine tracheal smooth muscle. Biophys J 59: 58a 1991

    Google Scholar 

  55. Martson SB, Pritchard K, Rediwood C, Taggart M: Ca2+ regulation of thin filaments: biochemical mechanisms and physiological role. Biochem Soc Trans 16: 494–497, 1988

    Google Scholar 

  56. Sobue K, Takahashi K, Tanaka T, Kanda K, Ashino N, Kakiuchi S, Maruyama K: Crosslinking of actin filaments is caused by caldesmon aggregates, but not by its dimers. FEBS Lett 182: 201–204, 1985

    Google Scholar 

  57. Silver PJ, Stull JT: Regulation of myosin light chain and phosphorylase phosphorylation in tracheal smooth muscle. J Biol Chem 257: 6145–6150, 1982

    Google Scholar 

  58. Berridge MJ: Inositol trisphosphate and diacylglycerol as second messengers. Biochem J 220: 345–360, 1984

    Google Scholar 

  59. Stabel S, Parker PJ: Protein kinase C. Pharmacol Ther 51: 71–95, 1991

    Google Scholar 

  60. DeVries G, Fraser ED, Walsh MP: Protein kinase C from chicken eizzard: Characterization and detection of an inhibitor and endogenous substrates. Biochem Cell Biol 67: 260–270, 1989

    Google Scholar 

  61. Haller H, Smallwood JI, Rasmussen H: Protein kinase C translocation in intact vascular smooth muscle strips. Biochem J 270: 375–381, 1990

    Google Scholar 

  62. Rembold CM, Murphy RA: [Ca2+]-dependent myosin phosphorylation in phorbal diester stimulated smooth muscle contraction. Am J Physiol 255: C719-C723, 1988

    Google Scholar 

  63. Jiang, MJ, Morgan KG: Intercellular calcium levels in phorbal esterinduced contractions of vascular muscle. Am J Physiol 253: H1365-H1371, 1987

    Google Scholar 

  64. Itoh H, Lederis K: Contraction of rat thoracic aorta strips induced by phorbal 12-myristate 13-acetate. Am J Physiol 252: C244-C247, 1987

    Google Scholar 

  65. Katsuyama H, Morgan KG: Mechanisms of Ca2+-independent contraction in single permeabilized ferret aorta cells. Circ Res 72: 651–657, 1993

    Google Scholar 

  66. Pritchard K, Moody CJ: Caldesmon: a calmodulin-binding actinregulatory protein. Cell Calcium 7: 309–328, 1986

    Google Scholar 

  67. Small JV, Frust DO, DeMeys J: LOcalization of filamin in smooth muscle. J Cell Biol 102: 210–220, 1989

    Google Scholar 

  68. Rasmussen H, Kelley G, Douglas JS: Interactions between Ca2+ and cAMP messenger system in regulation of airway smooth muscle contraction. Am J Physiol 258 (Lung Cell Mol Physiol 2): L279-L288, 1990

    Google Scholar 

  69. Morgan JP, Morgan KG: Vascular smooth muscle: The first record Ca2+ transients. Pflüger Arch 395: 75–77, 1982

    Google Scholar 

  70. Morgan JP, Morgan KG: Alteration of cytoplasmic ionized calcium level in smooth muscle by vasodilators in the ferret. J Physiol 357: 539–551, 1984

    Google Scholar 

  71. Kobayashi S, Kitazawa T, Somlyo AV, Somlyo AP: Cytosolic heparin inhibits muscarinic and a-adrenergic Ca2+ release in smooth muscle. Physiological role of inositol 1,4,5-trisphosphate in pharmacolmechanical coupling. J Biol Chem 264: 17997–18004, 1989

    Google Scholar 

  72. Nishimura J, Moreland S, Moreland RS and Van Breemen C: Regulation of the Ca2+-force relationship in permeabilized arterial smooth muscle. In: R.S. Moreland (ed.) Regulation of Smooth Muscle Contraction. Plenum Press, New York, 1991, pp 111–127

    Google Scholar 

  73. Kitazawa T, Kobayashi S, Horiuchi K, Somlyo AV and Somlyo AP: Receptor coupled, permeabilized smooth muscle: Role of the phosphatidylinositol cascade, G-proteins and modulation of the contractile response to Ca2+. J Biol Chem 264: 5339–5342, 1989

    Google Scholar 

  74. Nishimura J, Khalil RA, Drenth JP, Van Breemen C: Evidence for increased myofilament Ca2+ sensitivity in norepinephrine-activated vascular smooth muscle. Am J Physiol 259 (Heart Circ Physiol 28): H2-H8, 1990

    Google Scholar 

  75. Fujiwara T, Itoh T, Kubota Y, Kuriyama H: Effects of guanosine nucleotides on skinned smooth muscle tissue of the rabbit mesenteric artery. J Physiol (Lond) 408: 535–547, 1989

    Google Scholar 

  76. Nishimura J, Kolber M, Van Breeman C: Norepinephrine and GTP-gamma-S increase myofilaments Ca2+ sensitivity in a-toxin permeabilized arterial smooth muscle. Biochem Biophys Res Commun 157: 677–683, 1988

    Google Scholar 

  77. Kubota Y, Kamm KE, Stull JT: Mechanism of GTP-gamma-S-dependent regulation of smooth muscle contraction. Biophys J 57: 152a, 1990

    Google Scholar 

  78. Stull JT, Tansey MG, Word A, Kubota Y, Kamm KE: Myosin light chain kinase phosphorylation: regulation of the Ca2+ sensitivity of contractile elements. In: R.S. Moreland (ed). Regulation of Smooth Muscle Contraction. Plenum Press, New York, 1991b, pp 129–138

    Google Scholar 

  79. Pritchard K, Marston SB: The Ca2+-sensitizing component of smooth muscle thin filaments properties of regulatory factors that interact with caldesmon. Biochem Biophys Res Commun 190: 668–673, 1993

    Google Scholar 

  80. Barron JT, Bàràny M, Bàràny K: Phosphorylation of the 20,000-dalton light chain of myosin of intact smooth muscle in rest and in contraction. J Bio Chem 254: 4954–4956, 1979

    Google Scholar 

  81. Hoar PE, Kerick EGL, Cassidy PS: Chicken gizzard: relation between calcium-activated phosphorylation and contraction. Science 204: 503–506, 1979

    Google Scholar 

  82. Driska SP, Aksoy ML, Murphy RA: Myosin light chain phosphorylation associated with contraction in arterial smooth muscle. Am J Physiol 240: C222-C233, 1981

    Google Scholar 

  83. Butler TM, Siegman MJ, Moores SU: Chemical energy usage during shortening and work production in mammalian smooth muscle. Am J Physiol 244 (Cell Physiol 13): C234-C242, 1983

    Google Scholar 

  84. Moreland S, Moreland R, Singer MA: Apparent dissociation between myosin light chain phosphorylation and maximal velocity of shortening in KCl depolarized swine carotid artery: effect of temperature and KCl concentration. Pflügers Arch 408: 139–145, 1986

    Google Scholar 

  85. Merkel L, Gerthoffer WT, Torphy TJ: Dissociation between myosin phosphorylation and shortening velocity in canine trachea. Am J Physiol 259 (Cell Physiol 27): C524-C532, 1990

    Google Scholar 

  86. Jiang H, Kang Rao, Halayko AJ, Kepron W, Stephens NL: Bronchial smooth muscle mechanics of a canine model of allergic airway hyperresponsiveness. J Appl Physiol 72(1): 39–45, 1992a

    Google Scholar 

  87. Taylor SR, Rudel R: Striated muscle fibers: inactivation of contraction induced by shortening. Science 167: 882–884, 1970

    Google Scholar 

  88. Jewell BR. In: The Physiological Basis of Starling's Law of the Heart, Ciba Symposium: 24, Elsevier, Amsterdam, p 109–111

  89. Stephens NL, Mitchell RW. In: N.L. Stephens (ed). Smooth Muscle Contraction. Marcel Dekker, New York, 1984, pp 91–112

    Google Scholar 

  90. Hai C-M: Length-dependent myosin phosphorylation and contraction of arterial smooth muscle. Pflügers Arch 418: 564–571, 1991

    Google Scholar 

  91. Jiang H, Rao K, Liu X, Halayko AJ, Stephens NL: Myosin light chain phosphorylation is smooth muscle length dependent. Biophys J 61 (2 pt): 2): A16, 1992b

    Google Scholar 

  92. Cheng R, Babu A, Fein F, Sonnenblick E, Su H, Gulati J: Evidence ter symmetric and asymmetric extractions using biotinylated TnC and rhodamine avidin: Polarity of the thin filament as the mechanism of length transduction in the modulation of Ca2+ sensitivity. FASEB J 6(1): A294, 1992

    Google Scholar 

  93. Walsh Jr. JV, Singer JJ: Calcium action potentials in single freshly isolated smooth muscle cells. Am J Physiol 239: C162–174, 1980

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Physiology, Faculty of Medicine, University of Manitoba, 770 Bannatyne Avenue, R3E OW3, Winnipeg, Manitoba, Canada

    He Jiang & Newman L. Stephens

Authors
  1. He Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Newman L. Stephens
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jiang, H., Stephens, N.L. Calcium and smooth muscle contraction. Mol Cell Biochem 135, 1–9 (1994). https://doi.org/10.1007/BF00925956

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00925956

Key words

Search

Navigation