Molecular and Cellular Biochemistry

, Volume 85, Issue 1, pp 75–791 | Cite as

Effect of calmodulin on sarcoplasmic reticular Ca2+-transport in the aging heart

  • Clayton E. Heyliger
  • Allan R. Prakash
  • John H. McNeill
Original Article

Abstract

Heart failure is common among the elderly and an alteration in myocardial Ca2+ transport is believed to be involved in its depressed contractile performance. Although ATP-dependent sarcoplasmic reticular (SR) Ca2+ transport has been reported to decrease in old hearts, virtually nothing appears to be known about the Ca2+ pump activity of SR in aging myocardium in the presence of calmodulin, one of its endogenous activators. In this study, the activity of the Ca2+ pump of aging cardiac SR was assessed in the presence of this endogenous stimulator. This assessment was therefore designed to give additional information about the status of this enzyme in old hearts. Male Sprague-Dawley rats were used and were divided into 3 groups: young (4–6 months old); middle-aged (15–17 months old) and old age (24–25 months old). Purified SR membranes were isolated from ventricular tissues. ATP-dependent Ca2+ accumulation by membrane vesicles of middle-aged and old hearts was significantly depressed in comparison to young hearts at all Ca2+ concentrations employed in the absence and presence of calmodulin. The activity of this Ca2+ transporter was similar in middle-aged and old hearts even in the presence of calmodulin. These results suggest that the activity of the Ca2+ pump in SR of aging hearts is depressed even in the presence of calmodulin.

Key words

aging myocardium Ca2+ pump sarcoplasmic reticulum calmodulin Ca2+ uptake 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Baskin SI, Uricchion FJ, Kendrick ZV: The effect of age in the regional distribution of four cations in the rat heart. Age 2:64–67, 1979Google Scholar
  2. 2.
    Capasso JM, Malhotra A, Remily RM, Scheuer J, Sonnenblick EH: Effect of age on mechanical and electrical performance of rat myocardium. Am J Physiol 245:H72-H81, 1983Google Scholar
  3. 3.
    Froehlich JP, Lakatta EG, Beard E, Spurgeon HA, Weisfeldt ML, Gerstenblith G: Studies of sarcoplasmic reticulum function and contraction duration in young adult and aged rat myocardium. J Mol Cell Cardiol 10:427–438, 1987Google Scholar
  4. 4.
    Narayanan N: Differential alternations in ATP-supported calcium transport activities of sarcoplasmic reticulum and sarcolemma of aging myocardium. Biochem Biophys Acta 678:442–459, 1981Google Scholar
  5. 5.
    Narayanan N: Comparison of ATP-dependent calcium transport and calcium activated ATPase activities of cardiac sarcoplasmic reticulum and sarcolemma from rats of various ages. Mechanisms of Aging and Development 38:127–143, 1987Google Scholar
  6. 6.
    Dhalla NS, Pierce GN, Panagia V, Singal PK, Beamish RE: Calcium movements in relation to heart function. Basic Res Cardiol 77:117–139, 1982Google Scholar
  7. 7.
    Carafoli E: Calmodulin in membrane transport of Ca2+. Cell Calcium 2:353–363, 1981Google Scholar
  8. 8.
    Lindemann JP, Watanabe AM: Phosphorylation of phospholamban in intact myocardium: role of Ca2+-calmodulin-dependent mechanisms. J Biol Chem 260:4516–4525, 1985Google Scholar
  9. 9.
    Lopaschuk G, Richter B, Katz S: Characterization of calmodulin effects on calcium transport in cardiac microsomes enriched in sarcoplasmic reticulum. Biochemistry 19:5603–5607, 1980Google Scholar
  10. 10.
    McConnaughey MM, Jones LIZ, Watanabe AM, Besch HR Jr, Williams LT, Lefkowitz RJ: Thyroxine and propylthiouracil effects on alpha- and beta-adrenergic receptor number, ATPase activities and sialic acid content of rat cardiac membrane vesicles. J Cardiovasc Pharmacol 1:608–623, 1979Google Scholar
  11. 11.
    Lowry OH, Rosebrough NJ, Farr AL, Randall RJ: Protein measurement with the folin phenol reagent. J Biol Chem 193:265–275, 1951PubMedGoogle Scholar
  12. 12.
    Kirchberger MA, Tada M, Katz AM: Adenosine 3′:5′-monophosphate-dependent protein kinase-catalyzed phosphorylation reaction and its relationship to calcium transport in cardiac sarcoplasmic reticulum. J Biol Chem 249:6166–6173, 1974Google Scholar
  13. 13.
    Caroni P, Carafoli E: The Ca2+-pumping ATPase of heart sarcolemma: characterization, calmodulin dependence and partial purification. J Biol Chem 256:3263–3270, 1981Google Scholar
  14. 14.
    Adams RJ, Schwartz A: Comparative mechanisms for contraction of cardiac and skeletal muscle. Chest 78:1235–1395, 1980Google Scholar
  15. 15.
    Tuana BS, Dzurba A, Panagia V, Dhalla NS: 1Stimulation of heart sarcolemmal calcium pump by calmodulin. Biochem Biophys Res Commun 100:1245–1250, 1981Google Scholar

Copyright information

© Kluwer Academic Publishers 1989

Authors and Affiliations

  • Clayton E. Heyliger
    • 1
  • Allan R. Prakash
    • 1
  • John H. McNeill
    • 1
  1. 1.Division of Pharmacology and ToxicologyFaculty of Pharmaceutical Sciences, University of British ColumbiaVancouverCanada

Personalised recommendations