Skip to main content
PMC home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1994 Nov;113(3):1001–1007. doi: 10.1111/j.1476-5381.1994.tb17092.x

Effect of cyclopiazonic acid, an inhibitor of sarcoplasmic reticulum Ca(2+)-ATPase, on the frequency-dependence of the contraction-relaxation cycle of the guinea-pig isolated atrium.

N J Yard 1, M Chiesi 1, H A Ball 1
PMCID: PMC1510447  PMID: 7858841

Abstract

1. The relevance of a functional sarcoplasmic reticulum (SR) membrane system to the contraction-relaxation cycle and to the force-frequency relationship of guinea-pig atrial tissue was investigated. Cyclopiazonic acid (CPA) was used to inhibit selectively the activity of the SR Ca(2+)-ATPase. IC50 values of 0.2 microM or 1.0 microM were measured in guinea-pig isolated SR membranes in the absence or presence of millimolar ATP, respectively. CPA (0.3-30 microM) did not inhibit the activity of the sarcolemmal Na(+)-Ca(2+)-exchanger as measured in isolated cardiac cell membrane preparations. 2. In guinea-pig isolated left atrium paced at 2.5 Hz (30 degrees C), CPA (1-100 microM) produced a concentration-dependent reduction in developed tension and a fall in the maximum rate of tension increase (+dT/dtmax) and decrease (-dT/dtmax). The twitch duration was markedly increased due to a prolongation of the time to peak tension, and in particular, the relaxation phase. 3. The contraction-relaxation cycle of the left atrium showed a marked dependence on the frequency of stimulation. The developed tension and +dT/dtmax showed a progressive increase from 0.5 Hz, reaching peak values at a stimulation rate of 1.5-2.5 Hz, the positive staircase phenomenon. Higher frequencies of stimulation caused a fall in these parameters. Resting tension was unaffected. The time-course of the contraction-relaxation cycle was also frequency-dependent, with both time to peak tension and relaxation time showing a progressive fall from 2.0-3.5 Hz. 4. The addition of CPA (30 microM) caused marked alterations in the frequency-dependence of the contraction-relaxation cycle.(ABSTRACT TRUNCATED AT 250 WORDS)

Full text

PDF

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aceto J. F., Condrescu M., Kroupis C., Nelson H., Nelson N., Nicoll D., Philipson K. D., Reeves J. P. Cloning and expression of the bovine cardiac sodium-calcium exchanger. Arch Biochem Biophys. 1992 Nov 1;298(2):553–560. doi: 10.1016/0003-9861(92)90449-7. [DOI] [PubMed] [Google Scholar]
  2. Arai M., Alpert N. R., MacLennan D. H., Barton P., Periasamy M. Alterations in sarcoplasmic reticulum gene expression in human heart failure. A possible mechanism for alterations in systolic and diastolic properties of the failing myocardium. Circ Res. 1993 Feb;72(2):463–469. doi: 10.1161/01.res.72.2.463. [DOI] [PubMed] [Google Scholar]
  3. Beuckelmann D. J., Näbauer M., Erdmann E. Intracellular calcium handling in isolated ventricular myocytes from patients with terminal heart failure. Circulation. 1992 Mar;85(3):1046–1055. doi: 10.1161/01.cir.85.3.1046. [DOI] [PubMed] [Google Scholar]
  4. Bourreau J. P., Abela A. P., Kwan C. Y., Daniel E. E. Acetylcholine Ca2+ stores refilling directly involves a dihydropyridine-sensitive channel in dog trachea. Am J Physiol. 1991 Sep;261(3 Pt 1):C497–C505. doi: 10.1152/ajpcell.1991.261.3.C497. [DOI] [PubMed] [Google Scholar]
  5. Brandl C. J., Green N. M., Korczak B., MacLennan D. H. Two Ca2+ ATPase genes: homologies and mechanistic implications of deduced amino acid sequences. Cell. 1986 Feb 28;44(4):597–607. doi: 10.1016/0092-8674(86)90269-2. [DOI] [PubMed] [Google Scholar]
  6. Buckley N. M., Penefsky Z. J., Litwak R. S. Comparative force-frequency relationships in human and other mammalian ventricular myocardium. Pflugers Arch. 1972;332(4):259–270. doi: 10.1007/BF00588574. [DOI] [PubMed] [Google Scholar]
  7. Carafoli E. Intracellular calcium homeostasis. Annu Rev Biochem. 1987;56:395–433. doi: 10.1146/annurev.bi.56.070187.002143. [DOI] [PubMed] [Google Scholar]
  8. Chamberlain B. K., Levitsky D. O., Fleischer S. Isolation and characterization of canine cardiac sarcoplasmic reticulum with improved Ca2+ transport properties. J Biol Chem. 1983 May 25;258(10):6602–6609. [PubMed] [Google Scholar]
  9. Chiesi M., Inesi G. The use of quench reagents for resolution of single transport cycles in sarcoplasmic reticulum. J Biol Chem. 1979 Oct 25;254(20):10370–10377. [PubMed] [Google Scholar]
  10. Deng H. W., Kwan C. Y. Cyclopiazonic acid is a sarcoplasmic reticulum Ca(2+)-pump inhibitor of rat aortic muscle. Zhongguo Yao Li Xue Bao. 1991 Jan;12(1):53–58. [PubMed] [Google Scholar]
  11. Goeger D. E., Riley R. T. Interaction of cyclopiazonic acid with rat skeletal muscle sarcoplasmic reticulum vesicles. Effect on Ca2+ binding and Ca2+ permeability. Biochem Pharmacol. 1989 Nov 15;38(22):3995–4003. doi: 10.1016/0006-2952(89)90679-5. [DOI] [PubMed] [Google Scholar]
  12. Gwathmey J. K., Copelas L., MacKinnon R., Schoen F. J., Feldman M. D., Grossman W., Morgan J. P. Abnormal intracellular calcium handling in myocardium from patients with end-stage heart failure. Circ Res. 1987 Jul;61(1):70–76. doi: 10.1161/01.res.61.1.70. [DOI] [PubMed] [Google Scholar]
  13. Gwathmey J. K., Slawsky M. T., Hajjar R. J., Briggs G. M., Morgan J. P. Role of intracellular calcium handling in force-interval relationships of human ventricular myocardium. J Clin Invest. 1990 May;85(5):1599–1613. doi: 10.1172/JCI114611. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hasenfuss G., Mulieri L. A., Leavitt B. J., Allen P. D., Haeberle J. R., Alpert N. R. Alteration of contractile function and excitation-contraction coupling in dilated cardiomyopathy. Circ Res. 1992 Jun;70(6):1225–1232. doi: 10.1161/01.res.70.6.1225. [DOI] [PubMed] [Google Scholar]
  15. Hilgemann D. W., Noble D. Excitation-contraction coupling and extracellular calcium transients in rabbit atrium: reconstruction of basic cellular mechanisms. Proc R Soc Lond B Biol Sci. 1987 Mar 23;230(1259):163–205. doi: 10.1098/rspb.1987.0015. [DOI] [PubMed] [Google Scholar]
  16. Jones L. R. Rapid preparation of canine cardiac sarcolemmal vesicles by sucrose flotation. Methods Enzymol. 1988;157:85–91. doi: 10.1016/0076-6879(88)57070-2. [DOI] [PubMed] [Google Scholar]
  17. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  18. Lewartowski B., Pytkowski B. Cellular mechanism of the relationship between myocardial force and frequency of contractions. Prog Biophys Mol Biol. 1987;50(2):97–120. doi: 10.1016/0079-6107(87)90005-8. [DOI] [PubMed] [Google Scholar]
  19. Mercadier J. J., Lompré A. M., Duc P., Boheler K. R., Fraysse J. B., Wisnewsky C., Allen P. D., Komajda M., Schwartz K. Altered sarcoplasmic reticulum Ca2(+)-ATPase gene expression in the human ventricle during end-stage heart failure. J Clin Invest. 1990 Jan;85(1):305–309. doi: 10.1172/JCI114429. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Mulieri L. A., Hasenfuss G., Leavitt B., Allen P. D., Alpert N. R. Altered myocardial force-frequency relation in human heart failure. Circulation. 1992 May;85(5):1743–1750. doi: 10.1161/01.cir.85.5.1743. [DOI] [PubMed] [Google Scholar]
  21. Nicoll D. A., Longoni S., Philipson K. D. Molecular cloning and functional expression of the cardiac sarcolemmal Na(+)-Ca2+ exchanger. Science. 1990 Oct 26;250(4980):562–565. doi: 10.1126/science.1700476. [DOI] [PubMed] [Google Scholar]
  22. Nuss H. B., Houser S. R. Sodium-calcium exchange-mediated contractions in feline ventricular myocytes. Am J Physiol. 1992 Oct;263(4 Pt 2):H1161–H1169. doi: 10.1152/ajpheart.1992.263.4.H1161. [DOI] [PubMed] [Google Scholar]
  23. Penefsky Z. J., Buckley N. M., Litwak R. S. Effect of temperature and calcium on force-frequency relationships in mammalian ventricular myocardium. Pflugers Arch. 1972;332(4):271–282. doi: 10.1007/BF00588575. [DOI] [PubMed] [Google Scholar]
  24. Reiter M. Der Einfluss der Natriumionen auf die Beziehung zwischen Frequenz und Kraft der Kontraktion des isolierten Meerschweinchenmyokards. Naunyn Schmiedebergs Arch Pharmakol Exp Pathol. 1966;254(3):261–286. [PubMed] [Google Scholar]
  25. Schuler G., Hambrecht R., Schlierf G., Niebauer J., Hauer K., Neumann J., Hoberg E., Drinkmann A., Bacher F., Grunze M. Regular physical exercise and low-fat diet. Effects on progression of coronary artery disease. Circulation. 1992 Jul;86(1):1–11. doi: 10.1161/01.cir.86.1.1. [DOI] [PubMed] [Google Scholar]
  26. Seidler N. W., Jona I., Vegh M., Martonosi A. Cyclopiazonic acid is a specific inhibitor of the Ca2+-ATPase of sarcoplasmic reticulum. J Biol Chem. 1989 Oct 25;264(30):17816–17823. [PubMed] [Google Scholar]
  27. Seiler S., Fleischer S. Isolation and characterization of sarcolemmal vesicles from rabbit fast skeletal muscle. Methods Enzymol. 1988;157:26–36. doi: 10.1016/0076-6879(88)57065-9. [DOI] [PubMed] [Google Scholar]
  28. Suzuki M., Muraki K., Imaizumi Y., Watanabe M. Cyclopiazonic acid, an inhibitor of the sarcoplasmic reticulum Ca(2+)-pump, reduces Ca(2+)-dependent K+ currents in guinea-pig smooth muscle cells. Br J Pharmacol. 1992 Sep;107(1):134–140. doi: 10.1111/j.1476-5381.1992.tb14475.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Wier W. G., Yue D. T. Intracellular calcium transients underlying the short-term force-interval relationship in ferret ventricular myocardium. J Physiol. 1986 Jul;376:507–530. doi: 10.1113/jphysiol.1986.sp016167. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES