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. 1987 Nov 1;90(5):609–623. doi: 10.1085/jgp.90.5.609

Maximal Ca2+-activated force and myofilament Ca2+ sensitivity in intact mammalian hearts. Differential effects of inorganic phosphate and hydrogen ions

PMCID: PMC2228875  PMID: 3694173

Abstract

Myofilament Ca2+ sensitivity and maximal Ca2+-activated force are fundamental properties of the contractile proteins in the heart. Although these properties can be evaluated directly in skinned preparations, they have remained elusive in intact tissue. A novel approach is described that allows maximal Ca2+-activated force to be measured and myofilament Ca2+ sensitivity to be deduced from isovolumic pressure in intact perfused ferret hearts. Phosphorus nuclear magnetic resonance spectra are obtained sequentially to measure the intracellular inorganic phosphate (Pi) and hydrogen ion (H+) concentrations. After a period of perfusion with oxygenated, HEPES- buffered Tyrode solution, hypoxia is induced as a means of elevating [Pi]. The decline in twitch pressure can then be related to the measured increase in [Pi]. After recovery, hearts are perfused with ryanodine to enable tetanization and the measurement of maximal Ca2+- activated pressure. Hypoxia is induced once again, and maximal pressure is correlated with [Pi]. We then compare the relations between [Pi] and maximal pressure on the one hand, and [Pi] and twitch pressure on the other. If the two relations differ only by a constant scaling factor, then the decline in twitch pressure can be attributed solely to a decline in maximal pressure, with no change in myofilament sensitivity. We obtained such a result during hypoxia, which indicated that Pi accumulation decreases maximal force but does not change myofilament sensitivity. We compared these results with acidosis (induced by bubbling with 5% CO2). In contrast with Pi, the accumulation of H+ decreases twitch force primarily by shifting myofilament Ca2+ sensitivity. This approach in intact tissue has strengths and limitations complementary to those of skinned muscle experiments.

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Selected References

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  1. Allen D. G., Morris P. G., Orchard C. H., Pirolo J. S. A nuclear magnetic resonance study of metabolism in the ferret heart during hypoxia and inhibition of glycolysis. J Physiol. 1985 Apr;361:185–204. doi: 10.1113/jphysiol.1985.sp015640. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Allen D. G., Orchard C. H. Intracellular calcium concentration during hypoxia and metabolic inhibition in mammalian ventricular muscle. J Physiol. 1983 Jun;339:107–122. doi: 10.1113/jphysiol.1983.sp014706. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Allen D. G., Orchard C. H. The effects of changes of pH on intracellular calcium transients in mammalian cardiac muscle. J Physiol. 1983 Feb;335:555–567. doi: 10.1113/jphysiol.1983.sp014550. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brandt P. W., Cox R. N., Kawai M., Robinson T. Effect of cross-bridge kinetics on apparent Ca2+ sensitivity. J Gen Physiol. 1982 Jun;79(6):997–1016. doi: 10.1085/jgp.79.6.997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Burt C. T., Cohen S. M., Bárány M. Analysis with intact tissue with 31P NMR. Annu Rev Biophys Bioeng. 1979;8:1–25. doi: 10.1146/annurev.bb.08.060179.000245. [DOI] [PubMed] [Google Scholar]
  6. Donaldson S. K., Hermansen L., Bolles L. Differential, direct effects of H+ on Ca2+ -activated force of skinned fibers from the soleus, cardiac and adductor magnus muscles of rabbits. Pflugers Arch. 1978 Aug 25;376(1):55–65. doi: 10.1007/BF00585248. [DOI] [PubMed] [Google Scholar]
  7. Fabiato A., Fabiato F. Effects of pH on the myofilaments and the sarcoplasmic reticulum of skinned cells from cardiace and skeletal muscles. J Physiol. 1978 Mar;276:233–255. doi: 10.1113/jphysiol.1978.sp012231. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fabiato A. Myoplasmic free calcium concentration reached during the twitch of an intact isolated cardiac cell and during calcium-induced release of calcium from the sarcoplasmic reticulum of a skinned cardiac cell from the adult rat or rabbit ventricle. J Gen Physiol. 1981 Nov;78(5):457–497. doi: 10.1085/jgp.78.5.457. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Flaherty J. T., Weisfeldt M. L., Bulkley B. H., Gardner T. J., Gott V. L., Jacobus W. E. Mechanisms of ischemic myocardial cell damage assessed by phosphorus-31 nuclear magnetic resonance. Circulation. 1982 Mar;65(3):561–570. doi: 10.1161/01.cir.65.3.561. [DOI] [PubMed] [Google Scholar]
  10. Gadian D. G. Whole organ metabolism studied by NMR. Annu Rev Biophys Bioeng. 1983;12:69–89. doi: 10.1146/annurev.bb.12.060183.000441. [DOI] [PubMed] [Google Scholar]
  11. Hibberd M. G., Dantzig J. A., Trentham D. R., Goldman Y. E. Phosphate release and force generation in skeletal muscle fibers. Science. 1985 Jun 14;228(4705):1317–1319. doi: 10.1126/science.3159090. [DOI] [PubMed] [Google Scholar]
  12. Ingwall J. S. Phosphorus nuclear magnetic resonance spectroscopy of cardiac and skeletal muscles. Am J Physiol. 1982 May;242(5):H729–H744. doi: 10.1152/ajpheart.1982.242.5.H729. [DOI] [PubMed] [Google Scholar]
  13. Katz A. M., Hecht H. H. Editorial: the early "pump" failure of the ischemic heart. Am J Med. 1969 Oct;47(4):497–502. doi: 10.1016/0002-9343(69)90180-6. [DOI] [PubMed] [Google Scholar]
  14. Kentish J. C. The effects of inorganic phosphate and creatine phosphate on force production in skinned muscles from rat ventricle. J Physiol. 1986 Jan;370:585–604. doi: 10.1113/jphysiol.1986.sp015952. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kusuoka H., Weisfeldt M. L., Zweier J. L., Jacobus W. E., Marban E. Mechanism of early contractile failure during hypoxia in intact ferret heart: evidence for modulation of maximal Ca2+-activated force by inorganic phosphate. Circ Res. 1986 Sep;59(3):270–282. doi: 10.1161/01.res.59.3.270. [DOI] [PubMed] [Google Scholar]
  16. Kübler W., Katz A. M. Mechanism of early "pump" failure of the ischemic heart: possible role of adenosine triphosphate depletion and inorganic phosphate accumulation. Am J Cardiol. 1977 Sep;40(3):467–471. doi: 10.1016/0002-9149(77)90174-6. [DOI] [PubMed] [Google Scholar]
  17. Marban E., Kusuoka H., Yue D. T., Weisfeldt M. L., Wier W. G. Maximal Ca2+-activated force elicited by tetanization of ferret papillary muscle and whole heart: mechanism and characteristics of steady contractile activation in intact myocardium. Circ Res. 1986 Sep;59(3):262–269. doi: 10.1161/01.res.59.3.262. [DOI] [PubMed] [Google Scholar]
  18. Solaro R. J., Holroyde M. J., Herzig J. W., Peterson J. Cardiac relaxation and myofibrillar interactions with phosphate and vanadate. Eur Heart J. 1980;Suppl A:21–27. doi: 10.1093/eurheartj/1.suppl_1.21. [DOI] [PubMed] [Google Scholar]
  19. Solaro R. J., Kumar P., Blanchard E. M., Martin A. F. 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. 1986 May;58(5):721–729. doi: 10.1161/01.res.58.5.721. [DOI] [PubMed] [Google Scholar]
  20. Yue D. T., Marban E., Wier W. G. Relationship between force and intracellular [Ca2+] in tetanized mammalian heart muscle. J Gen Physiol. 1986 Feb;87(2):223–242. doi: 10.1085/jgp.87.2.223. [DOI] [PMC free article] [PubMed] [Google Scholar]

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