The Effects of Volatile Anesthetics on the Calcium Sensitivity of Cardiac Myofilaments

  • Isabelle Murat
  • Renée Ventura-Clapier
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 301)


Volatile anesthetics mainly depress myocardial contractility by their actions on sarcoplasmic reticulum function and on sarcolemmal ionic currents.1 A direct effect of volatile anesthetics on myocardial contractile proteins was first described by Merin in 1974,2 but this was only observed at rather high anesthetic concentrations. Skinned fiber preparations represent an unique model for studying the contractile apparatus itself. Studies on detergent-treated skinned fibers of various animal species have provided evidence for a volatile-anesthetic-induced decrease in both the calcium sensitivity and the maximal developed tension of cardiac myofilaments. These effects are dose-dependent, reversible and quantitatively equivalent for the three currently used anesthetics, halothane, enflurane, and isoflurane.3,4,5 This chapter will review the physiological properties of the contractile proteins and the experimental studies on volatile anesthetic effects.


Volatile Anesthetic Contractile Protein Sarcomere Length Calcium Sensitivity Anesthetic Concentration 
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.
    B. F. Rusy, H. Komai, Anesthetic depression of myocardial contractility: A review of possible mechanisms, Anesthesiology 67:745–766 (1987).PubMedCrossRefGoogle Scholar
  2. 2.
    R. G. Merin, T. Kumazawa, C. R. Honig, Reversible interaction between halothane and Ca2+ on cardiac adenosine triphosphatase: Mechanism and significance, J Pharmacol Exp Ther 190:1–14 (1974).PubMedGoogle Scholar
  3. 3.
    I. Murat, R. Ventura-Clapier, G. Vassort, Halothane, enflurane, and isoflurane decrease calcium sensitivity and maximal force in detergent treated rat cardiac fibers, Anesthesiology 69:892–899 (1988).PubMedCrossRefGoogle Scholar
  4. 4.
    I. Murat, V. I. Veksler, R. Ventura-Clapier, Effects of halothane on cardiac skinned fibers from cardiomyopathic animals, J Mol Cell Cardiol 21:1293–1304 (1989).PubMedCrossRefGoogle Scholar
  5. 5.
    I. Murat, J. Hoerter, R. Ventura-Clapier, Developmental changes in effects of halothane and isoflurane on contractile properties of rabbit cardiac skinned fibers, Anesthesiology 73:137–145 (1990).PubMedCrossRefGoogle Scholar
  6. 6.
    A. F. Huxley, R. M. Simmons, Proposed mechanism of force generation in striated muscle, Nature (Lond) 233:533–538 (1971).PubMedCrossRefGoogle Scholar
  7. 7.
    P. A. Hofmann, F. Fuchs, Evidence for a force-dependent component of calcium binding to cardiac troponin C, Am J Physiol 253:C541–C546 (1987).PubMedGoogle Scholar
  8. 8.
    M. J. Holroyde, S. P. Robertson, J. D. Johnson, R. J. Solaro, J. D. Potter, The calcium and magnesium binding sites on cardiac troponin and their role in the regulation of myofibrillar adenosine triphosphatase, J Biol Chem 255:11688–11693 (1980).PubMedGoogle Scholar
  9. 9.
    R. J. Solaro, R. M. Wise, J. S. Shiner, F. N. Briggs, Calcium requirements for cardiac myofibrillar activation, Circ Res 34:525–530 (1974).PubMedGoogle Scholar
  10. 10.
    A. Babu, E. Sonnenblick, J. Gulati, Molecular basis for the influence of muscle length on myocardial performance, Science 240:74–76 (1988).PubMedCrossRefGoogle Scholar
  11. 11.
    S. M. Harrison, C. Lamont, D. J. Miller, Hysteresis and the length dependence of calcium sensitivity in chemically skinned rat cardiac muscle, J Physiol (Lond) 401:115–144 (1988).PubMedGoogle Scholar
  12. 12.
    M. G. Hibberd, B. R. Jewell, Calcium-and length-dependent force production in rat ventricular muscle, J Physiol (Lond) 329:527–540 (1982).PubMedGoogle Scholar
  13. 13.
    J. C. Kentish, H. E. D. J. Ter Keurs, L. Ricciardi, J. J. J. Buck, M. I. M. Noble, Comparison between the sarcomere length-force relations of intact and skinned trabeculae from rat right ventricle. Influence of calcium concentrations on these relations, Circ Res 58:755–768 (1986).PubMedGoogle Scholar
  14. 14.
    S. M. Harrison, D. M. Bers, Influence of temperature on the calcium sensitivity of the myofilaments of skinned ventricular muscle from the rabbit, J Gen Physiol 93:411–428 (1989).PubMedCrossRefGoogle Scholar
  15. 15.
    A. Fabiato, F. Fabiato, Effects of pH on the myofilaments and the sarcoplasmic rcticulum of skinned cells from cardiac and skeletal muscles, J Physiol (Lond) 276:233–255 (1978).PubMedGoogle Scholar
  16. 16.
    R. J. Solaro, P. Kumar, E. M. Blanchard, A. F. Martin, Differential effects of pH on calcium activation of myofilaments of adult and perinatal dog hearts: Evidence for developmental differences in thin filament regulation, Circ Res 58:721–729 (1986).PubMedGoogle Scholar
  17. 17.
    R. J. Solaro, L. A. Lee, J. C. Kentish, D. G. Allen, Effects of acidosis on ventricular muscle from adult and neonatal rats, Circ Res 63:779–787 (1988).PubMedGoogle Scholar
  18. 18.
    J. C. Kentish, The inhibitory effects of monovalent ions on force development in detergent skinned ventricular muscle from guinea-pig, J Physiol (Lond) 352:353–374 (1984).PubMedGoogle Scholar
  19. 19.
    J. C. Kentish, The effects of inorganic phosphate and creatine phosphate on force production in skinned muscles from rat ventricle, J Physiol (Lond) 370:585–604 (1986).PubMedGoogle Scholar
  20. 20.
    H. Mekhfi, R. Ventura-Clapier, Dependence upon high-energy phosphates on the effects of inorganic phosphate on contractile properties in chemically skinned rat cardiac fibres, Pflügers Arch 411:378–385 (1988).PubMedCrossRefGoogle Scholar
  21. 21.
    P. M. Best, S. K. Bolitho Donaldson, W. G. L. Kerrick, Tension in mechanically disrupted mammalian cardiac cells: Effects of magnesium adenosine triphosphate, J Physiol (Lond) 265:1–17 (1977).PubMedGoogle Scholar
  22. 22.
    G. B. McClellan, S. Winegrad, The regulation of the calcium sensitivity of the contractile system in mammalian cardiac muscle. J Gen Physiol 72:737–764 (1978).PubMedCrossRefGoogle Scholar
  23. 23.
    S. Winegrad, G. McClellan, R. Horowits, M. Tucker, E. R. Lin, A. Weisberg, Regulation of cardiac contractile proteins by phosphorylation, Fed Proc 42:39–44 (1983)PubMedGoogle Scholar
  24. 24.
    I. Morano, F. Hofmann, M. Zimmer, J. C. Ruegg, The influence of P-light chain phosphorylation by myosin light chain kinase on the calcium sensitivity of chemically skinned heart fibres, FEBS Lett 189:221–224 (1985).PubMedCrossRefGoogle Scholar
  25. 25.
    A. Babu, W. Lehman, J. Gulati, Characterization of the Ca2+-switch in skeletal and cardiac muscles, FEBS Lett 251:177–182 (1989).PubMedCrossRefGoogle Scholar
  26. 26.
    S. P. Robertson, J. D. Johnson, M. J. Holroyde, E. G. Kranias, J. D. Potter, R. J. Solaro, The effect of troponin I phosphorylation on the Ca2+-binding properties of the Ca2+-regulatory site of bovine cardiac troponin, J Biol Chem 257:260–263 (1982).PubMedGoogle Scholar
  27. 27.
    F. H. Schachat, M. S. Diamond, P. W. Brandt, Effect of different troponin T-tropomyosin combinations on thin filament activation, J Mol Biol 198:551–554 (1987).PubMedCrossRefGoogle Scholar
  28. 28.
    A. S. Zot, J. D. Potter, Reciprocal coupling between troponin C and myosin crossbridge attachment, Biochemistry 28:6751–6756 (1989).PubMedCrossRefGoogle Scholar
  29. 29.
    R. Ventura-Clapier, H. Mekhfi, P. Oliviero, B. Swynghedauw, Pressure overload changes cardiac skinned fibers mechanics in rats not in guinea pigs, Am J Physiol 254:H517–H524 (1988).PubMedGoogle Scholar
  30. 30.
    W. E. Brodkin, A. H. Goldberg, H. L. Kayne, Depression of myofibrillar ATPase activity by halothane, Acta Anaesthesiol Scand 11:97–101 (1967).PubMedCrossRefGoogle Scholar
  31. 31.
    E. Leuwenkroon-Strösberg, L. H. Laasbcrg, J. Hcdley-White, Myosin conformation and enzymatic activity: Effect of chloroform, diethyl ether and halothane on optical rotatory dispersion and ATPase, Biochim Biophys Acta 295:178–186 (1973).PubMedGoogle Scholar
  32. 32.
    T. Ohnishi, G. S. Pressman, H. L. Price, A possible mechanism of anesthetic-induccd myocardial depression, Biochem Biophys Res Comm 57:316–322 (1974).CrossRefGoogle Scholar
  33. 33.
    H. T. Pask, P. J. England, C. Prys-Roberts, Effects of volatile inhalational anaesthetic agents on isolated bovine cardiac myolibrillar ATPase, J Mol Cell Cardiol 13:293–301 (1981).PubMedCrossRefGoogle Scholar
  34. 34.
    P. M. Best, Cardiac muscle function: Results from skinned fiber preparations, Am J Physiol 244:H167–H177 (1983).PubMedGoogle Scholar
  35. 35.
    J. Y. Su, W. G. L. Kerrick, Effects of halothane on Ca2+-activated tension development in mechanically disrupted rabbit myocardial fibers, Pflügers Arch 375:111–117 (1978).PubMedCrossRefGoogle Scholar
  36. 36.
    J. Y. Su, W. G. L. Kerrick, Effects of halothane on caffeine-induced tension transients in functionally skinned myocardial fibers, Pflügers Arch 380:597–604 (1979).CrossRefGoogle Scholar
  37. 37.
    J. Y. Su, W. G. L. Kerrick, Effects of cnflurane on functionally skinned myocardial fibers from rabbits, Anesthesiology 52:385–389 (1980).PubMedCrossRefGoogle Scholar
  38. 38.
    J. Y. Su, J. G. Bell, Intraccllular mechanism of action of isoflurane and halothane on striated muscle of the rabbit, Anesth Analg 65:457–462 (1986).PubMedCrossRefGoogle Scholar
  39. 39.
    D. J. Miller, H. Y. Elder, G. L. Smith, Ultrastructural and X-ray microanalysis studies of EGTA-and detergent-treated heart muscle, J Mol Cell Motility 6:525–540 (1985).CrossRefGoogle Scholar
  40. 40.
    E. J. Krane, J. Y. Su, Comparison of the effects of halothane on skinned myocardial fibers from newborn and adult rabbits: I. Contractile proteins, Anesthesiology 70:76–81 (1989).PubMedCrossRefGoogle Scholar
  41. 41.
    L. E. Ford, A. F. Huxley, R. M. Simmons, Tension responses to sudden length change in stimulated frog muscle fibers near slack length, J Physiol (Lond) 269:441–515 (1977).PubMedGoogle Scholar
  42. 42.
    L. E. Ford, A. F. Huxley, R. M. Simmons, The relation between stiffness and filament overlap in stimulated frog muscle fibers, J Physiol (Lond) 311:219–249 (1981).PubMedGoogle Scholar
  43. 43.
    I. Murat, P. Lechene, R. Ventura-Clapier, Effects of volatile anesthetics on mechanical properties of rat cardiac skinned fiber, Anesthesiology 73:73–81 (1990).PubMedCrossRefGoogle Scholar
  44. 44.
    E. S. Casella, T. J. J. Blanck, The effect of halothane on the binding of calcium by cardiac troponin C, Biophys J 53:583a (1988).Google Scholar
  45. 45.
    P. A. W. Anderson, G. E. Moore, R. N. Nassar, Developmental changes in the expression of rabbit left ventricular troponin T, Circ Res 63:742–747 (1988).PubMedGoogle Scholar
  46. 46.
    J. P. Jin, J. J. C. Lin, Rapid purification of mammalian cardiac troponin T and its isoform switching in rat hearts during development, J Biol Chem 263:7309–7315 (1988).PubMedGoogle Scholar
  47. 47.
    L. Saggin, S. Ausoni, L. Gorza, S. Sartore, S. Schiaffino, Troponin T switching in the developing rat heart, J Biol Chem 263:18488–18492 (1988).PubMedGoogle Scholar
  48. 48.
    L. Saggin, L. Gorza, S. Ausoni, S. Schiaffino, Troponin I switching in the developing heart. J Biol Chem 264:16299–16302 (1989).PubMedGoogle Scholar
  49. 49.
    L. S. Tobacman, R. Lee, Isolation and functional comparison of bovine cardiac troponin T isoforms, J Biol Chem 262:4059–4064 (1987).PubMedGoogle Scholar
  50. 50.
    J. M. Wilkinson, Troponin C from rabbit slow skeletal and cardiac muscle is a product of a single gene, Eur J Biochem 103:179–188 (1980).PubMedCrossRefGoogle Scholar
  51. 51.
    J. J. McAuliffe, L. Gao, R. J. Solaro, Changes in myofibrillar activation and troponin C Ca2+ binding associated with troponin T isoform switching in developing rabbit heart, Circ Res 66:1204–1216 (1990).PubMedGoogle Scholar
  52. 52.
    A. M. Lompré, J. J. Mercadier, C. Wisnewsky, P. Bouveret, C. Pantaloni, A. D’Albis, K. Schwartz, Species-and age-dependent changes in the relative amounts of cardiac myosin isoenzymes in mammals. Dev Biol 84:286–290 (1981).PubMedCrossRefGoogle Scholar
  53. 53.
    E. Eisenberg, T. L. Hill, Muscle contraction and free energy transduction in biological systems, Science 227:999–1006 (1985).PubMedCrossRefGoogle Scholar
  54. 54.
    P. R. Housmans, I. Murat, Comparative effects of halothane enflurane and isollurane at equipotent anesthetic concentrations on isolated ventricular myocardium of the ferret: I. Contractility, Anesthesiology 69:451–463 (1988).PubMedCrossRefGoogle Scholar
  55. 55.
    P. R. Housmans, I. Murat, Comparative effects of halothane enflurane and isofluranc on isolated ventricular myocardium of the ferret: II. Relaxation, Anesthesiology 69:464–471 (1988).PubMedCrossRefGoogle Scholar
  56. 56.
    D. L. Brutsaert, S. U. Sys, Relaxation and diastole of the heart, Physiol Rev 69:1228–1315 (1989).PubMedGoogle Scholar
  57. 57.
    P. R. Housmans, L. A. Wanek, E. G. Carton, Halothane (H), enilurane (E) and isoflurane (I) decrease myofibrillar Ca2+ responsiveness in intact mammalian ventricular muscle, Biophys J 57:554A (1990).Google Scholar
  58. 58.
    S. Ebashi, M. Endo, Calcium ion and muscle contraction, Prog Biophys Mol Biol 18:125–183 (1968).CrossRefGoogle Scholar
  59. 59.
    M. R. Berman, E. S. Casella, T. J. J. Blanck, Evidence for an effect of halothane on the maximum calcium-activated force generated by cardiac myofilaments, Anesthesiology 71:A250 (1989).CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Isabelle Murat
    • 1
  • Renée Ventura-Clapier
    • 2
  1. 1.Department of AnesthesiaHopital Saint-Vincent de PaulParisFrance
  2. 2.Laboratoire de Physiologie Cellulaire Cardiaque, INSERM U-241Universite Paris-SudOrsayFrance

Personalised recommendations