Genetic and non-genetic control of myocardial calcium

  • Norman R. Alpert
  • E. M. Blanchard
  • L. A. Mulieri
  • R. Nagai
  • A. Zarain-Herberg
  • M. Periasamy
Conference paper


Some aspects of the genetic and non-genetic control of the amount and rate of calcium cycled during steady-state activation of papillary muscles from right ventricular rabbit myocardium are presented. Genetic reorganization of the intracellular structure of the myocardium is achieved by producing right ventricular pressure overload and thyrotoxic hypertrophy. The mechanical performance of the pressure overload heart is slowed while time to peak tension is increased. These changes are associated with an increase in myothermal economy. In thyrotoxic hypertrophy the rate of mechanical performance is increased while time to peak tension is decreased. These alterations are associated with a decrease in myothermal economy. Tension-independent heat is used as an index of calcium cycling. In pressure overload hearts the amount and rate of calcium cycling is decreased. In contrast in thyrotoxic hypertrophy the amount of calcium cycled is unchanged while the rate is increased. In the pressure overload hearts there is a decrease in sarcoplasmic reticular (SR) Ca+ + ATPase, whereas in the thyrotoxic preparations the message is increased. The change in the rate of calcium uptake in pressure overload and thyrotoxic hearts is correlated with a change in the amount of SR Ca+ + ATPase mRNA. Calcium cycling was also altered by non-genetic inotropic intervention. Isoproterenol (1 µM) increases the amount of calcium cycled during each contraction relaxation cycle and the rate at which it is removed. These alterations are associated with an increase in force and a foreshortened twitch. Incubating the papillary muscle in high calcium (11 mM) also increases the force and the amount of calcium released into the cytosol. Unter these circumstances the rate of uptake is not significantly increased and, accordingly, the isometric twitch is not foreshortened. In the presence of verapamil (14 µM) the peak twitch force is decreased and the isometric myogram is foreshortened. These changes are associated with a decrease in the amount of calcium released during activation and the rate at which it is removed.


Calcium Uptake Papillary Muscle Pressure Overload Calcium Cycling Myocardial Calcium 
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  1. 1.
    Allen DG, Kentish JC (1985) The cellular basis of the length-tension relation in cardiac muscle. J Mol Cell Cardiol 17: 821–840PubMedCrossRefGoogle Scholar
  2. 2.
    Alpert NR, Mulieri LA (1982) Increased myothermal economy of isometric force generation in compensated cardiac hypertrophy induced by pulmonary artery constriction in the rabbit. Circ Res 50: 491–500PubMedCrossRefGoogle Scholar
  3. 3.
    Alpert NR, Mulieri LA (1984) Hypertrophic adaptation of the heart to stress: A myothermal analysis. In: Zak R (ed) Growth of the heart in health and disease. Raven Press, New York, pp 363–379Google Scholar
  4. 4.
    Alpert NR, Blanchard EM, Mulieri LA (1989) Tension Independent Heat in Rabbit Papillary Muscle. J Physiol (in press)Google Scholar
  5. 5.
    Banarjee SK, Flink IL, Morkin E (1976) Enzymatic properties of natural and N-ethylmaleimide modified cardiac myosin from normal and thyrotoxic rabbits. Circ Res 34: 319–326CrossRefGoogle Scholar
  6. 6.
    Blanchard EM, Mulieri LA, Alpert NR (1987) The effects of acute and chronic inotropic interventions on tension independent heat of rabbit papillary muscle. Basic Res Cardiol 82: Suppl 2, 127–135Google Scholar
  7. 7.
    Everrett AW, Clark WA, Chizzonite RA, Zak R (1983) Changes in synthesis rates of alpha and beta myosin heavy chains in rabbit heart after treatment with thyroid hormone. J Biol Chem 258: 2421–2425Google Scholar
  8. 8.
    Hamrell BB, Panannen R, Trono J, Alpert NR (1975) A stable, sensitive, low compliance capacitance force transducer. J Appl Physiol 38: 190–193PubMedGoogle Scholar
  9. 9.
    Hamrell BB, Alpert NR (1979) The mechanical characteristics of hypertrophied rabbit muscle cardiac muscle in the absence of congestive heart failure. Circ Res 40: 20–25CrossRefGoogle Scholar
  10. 11.
    Hill AV (1939) Recovery heat in muscle. Proc Roy Soc Lond (Biol) 127: 297–307CrossRefGoogle Scholar
  11. 12.
    Litten RZ, Martin BJ, Buchtal RH, Nagai R, Low RB, Alpert NR (1985) Heterogeneity of myosin isoenzyme content of rabbit heart. Circ Res 57: 406–414PubMedCrossRefGoogle Scholar
  12. 13.
    Morgan JP, Blinks JR (1982) Intracellular Ca++ transients in the cat papillary muscle. Can J Physiol Pharmacol 60: 524–528PubMedCrossRefGoogle Scholar
  13. 14.
    Mulieri LA, Luhr G, Trefry J, Alpert NR (1977) Metal-film thermopiles for use with rabbit right ventricular papillary muscles. Am J Physiol 233: C146 - C156PubMedGoogle Scholar
  14. 15.
    Nagai R, Pritzl N, Low RB, Stirewalt WS, Zak R, Alpert NR, Litten RZ (1987) Circ Res 60: 692–699PubMedCrossRefGoogle Scholar
  15. 16.
    Nagai R, Low RB, Stirewalt WS, Alpert NR, Litten RZ (1988) Efficiency and capacity of protein synthesis are increased in pressure overload cardiac hypertrophy. Am J Physiol 255: H325 - H328PubMedGoogle Scholar
  16. 17.
    Nagai R, Zarain-Herzberg A, Brandl CJ, Fujii J, Tada M, MacLennan DH, Alpert NR, Periasamy M (1989) Regulated expression of myocardial Ca+ + SR ATPase and Phospholamban in response to pressure overload and thyroid hormone. Proc National Academy of Sciences (in press)Google Scholar
  17. 18.
    Tada M, Kirchberger MA, Katz AM (1975) Phosphorylation of a 22000-dalton component of the cardiac sarcoplasmic reticulum by adenosine 3’:5’ monophosphate dependent protein kinase. J Biol Chem 250: 2640–2647PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1989

Authors and Affiliations

  • Norman R. Alpert
    • 2
  • E. M. Blanchard
    • 1
  • L. A. Mulieri
    • 1
  • R. Nagai
    • 1
  • A. Zarain-Herberg
    • 1
  • M. Periasamy
    • 1
  1. 1.Department of Physiology and BiophysicsUniversity of Vermont College of MedicineBurlingtonUSA
  2. 2.Department of Physiology and BiophysicsUniversity of Vermont College of MedicineBurlingtonUSA

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