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. 1995 Jan 1;105(1):1–19. doi: 10.1085/jgp.105.1.1

The relationship between contractile force and intracellular [Ca2+] in intact rat cardiac trabeculae

PMCID: PMC2216925  PMID: 7730787

Abstract

The control of force by [Ca2+] was investigated in rat cardiac trabeculae loaded with fura-2 salt. At sarcomere lengths of 2.1-2.3 microns, the steady state force-[Ca2+]i relationship during tetanization in the presence of ryanodine was half maximally activated at a [Ca2+]i of 0.65 +/- 0.19 microM with a Hill coefficient of 5.2 +/- 1.2 (mean +/- SD, n = 9), and the maximal stress produced at saturating [Ca2+]i equalled 121 +/- 35 mN/mm2 (n = 9). The dependence of steady state force on [Ca2+]i was identical in muscles tetanized in the presence of the Ca(2+)-ATPase inhibitor cyclopiazonic acid (CPA). The force-[Ca2+]i relationship during the relaxation of twitches in the presence of CPA coincided exactly to that measured at steady state during tetani, suggesting that CPA slows the decay rate of [Ca2+]i sufficiently to allow the force to come into a steady state with the [Ca2+]i. In contrast, the relationship of force to [Ca2+]i during the relaxation phase of control twitches was shifted leftward relative to the steady state relationship, establishing that relaxation is limited by the contractile system itself, not by Ca2+ removal from the cytosol. Under control conditions the force-[Ca2+]i relationship, quantified at the time of peak twitch force (i.e., dF/dt = 0), coincided fairly well with steady state measurements in some trabeculae (i.e., three of seven). However, the force-[Ca2+]i relationship at peak force did not correspond to the steady state measurements after the application of 5 mM 2,3-butanedione monoxime (BDM) (to accelerate cross-bridge kinetics) or 100 microM CPA (to slow the relaxation of the [Ca2+]i transient). Therefore, we conclude that the relationship of force to [Ca2+]i during physiological twitch contractions cannot be used to predict the steady state relationship.

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Selected References

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  1. Allen D. G., Kurihara S. Calcium transients in mammalian ventricular muscle. Eur Heart J. 1980;Suppl A:5–15. doi: 10.1093/eurheartj/1.suppl_1.5. [DOI] [PubMed] [Google Scholar]
  2. Allen D. G., Kurihara S. The effects of muscle length on intracellular calcium transients in mammalian cardiac muscle. J Physiol. 1982 Jun;327:79–94. doi: 10.1113/jphysiol.1982.sp014221. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Ashley C. C., Mulligan I. P., Lea T. J. Ca2+ and activation mechanisms in skeletal muscle. Q Rev Biophys. 1991 Feb;24(1):1–73. doi: 10.1017/s0033583500003267. [DOI] [PubMed] [Google Scholar]
  4. Backx P. H., Ter Keurs H. E. Fluorescent properties of rat cardiac trabeculae microinjected with fura-2 salt. Am J Physiol. 1993 Apr;264(4 Pt 2):H1098–H1110. doi: 10.1152/ajpheart.1993.264.4.H1098. [DOI] [PubMed] [Google Scholar]
  5. Baylor S. M., Hollingworth S. Fura-2 calcium transients in frog skeletal muscle fibres. J Physiol. 1988 Sep;403:151–192. doi: 10.1113/jphysiol.1988.sp017244. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Blinks J. R., Wier W. G., Hess P., Prendergast F. G. Measurement of Ca2+ concentrations in living cells. Prog Biophys Mol Biol. 1982;40(1-2):1–114. doi: 10.1016/0079-6107(82)90011-6. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Cobbold P. H., Rink T. J. Fluorescence and bioluminescence measurement of cytoplasmic free calcium. Biochem J. 1987 Dec 1;248(2):313–328. doi: 10.1042/bj2480313. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Fabiato A., Fabiato F. Effects of magnesium on contractile activation of skinned cardiac cells. J Physiol. 1975 Aug;249(3):497–517. doi: 10.1113/jphysiol.1975.sp011027. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fabiato A. Rapid ionic modifications during the aequorin-detected calcium transient in a skinned canine cardiac Purkinje cell. J Gen Physiol. 1985 Feb;85(2):189–246. doi: 10.1085/jgp.85.2.189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Godt R. E., Maughan D. W. Influence of osmotic compression on calcium activation and tension in skinned muscle fibers of the rabbit. Pflugers Arch. 1981 Oct;391(4):334–337. doi: 10.1007/BF00581519. [DOI] [PubMed] [Google Scholar]
  12. Grynkiewicz G., Poenie M., Tsien R. Y. A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem. 1985 Mar 25;260(6):3440–3450. [PubMed] [Google Scholar]
  13. Gwathmey J. K., Hajjar R. J. Relation between steady-state force and intracellular [Ca2+] in intact human myocardium. Index of myofibrillar responsiveness to Ca2+. Circulation. 1990 Oct;82(4):1266–1278. doi: 10.1161/01.cir.82.4.1266. [DOI] [PubMed] [Google Scholar]
  14. Güth K., Potter J. D. Effect of rigor and cycling cross-bridges on the structure of troponin C and on the Ca2+ affinity of the Ca2+-specific regulatory sites in skinned rabbit psoas fibers. J Biol Chem. 1987 Oct 5;262(28):13627–13635. [PubMed] [Google Scholar]
  15. Harrison S. M., Bers D. M. Correction of proton and Ca association constants of EGTA for temperature and ionic strength. Am J Physiol. 1989 Jun;256(6 Pt 1):C1250–C1256. doi: 10.1152/ajpcell.1989.256.6.C1250. [DOI] [PubMed] [Google Scholar]
  16. Harrison S. M., Bers D. M. Influence of temperature on the calcium sensitivity of the myofilaments of skinned ventricular muscle from the rabbit. J Gen Physiol. 1989 Mar;93(3):411–428. doi: 10.1085/jgp.93.3.411. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Harrison S. M., Lamont C., Miller D. J. Hysteresis and the length dependence of calcium sensitivity in chemically skinned rat cardiac muscle. J Physiol. 1988 Jul;401:115–143. doi: 10.1113/jphysiol.1988.sp017154. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Herrmann C., Wray J., Travers F., Barman T. Effect of 2,3-butanedione monoxime on myosin and myofibrillar ATPases. An example of an uncompetitive inhibitor. Biochemistry. 1992 Dec 8;31(48):12227–12232. doi: 10.1021/bi00163a036. [DOI] [PubMed] [Google Scholar]
  19. Higuchi H., Takemori S. Butanedione monoxime suppresses contraction and ATPase activity of rabbit skeletal muscle. J Biochem. 1989 Apr;105(4):638–643. doi: 10.1093/oxfordjournals.jbchem.a122717. [DOI] [PubMed] [Google Scholar]
  20. Hill T. L., Eisenberg E., Greene L. Theoretical model for the cooperative equilibrium binding of myosin subfragment 1 to the actin-troponin-tropomyosin complex. Proc Natl Acad Sci U S A. 1980 Jun;77(6):3186–3190. doi: 10.1073/pnas.77.6.3186. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Hofmann P. A., Fuchs F. Evidence for a force-dependent component of calcium binding to cardiac troponin C. Am J Physiol. 1987 Oct;253(4 Pt 1):C541–C546. doi: 10.1152/ajpcell.1987.253.4.C541. [DOI] [PubMed] [Google Scholar]
  22. Holroyde M. J., Robertson S. P., Johnson J. D., Solaro R. J., Potter J. D. The calcium and magnesium binding sites on cardiac troponin and their role in the regulation of myofibrillar adenosine triphosphatase. J Biol Chem. 1980 Dec 25;255(24):11688–11693. [PubMed] [Google Scholar]
  23. Kentish J. C. The inhibitory effects of monovalent ions on force development in detergent-skinned ventricular muscle from guinea-pig. J Physiol. 1984 Jul;352:353–374. doi: 10.1113/jphysiol.1984.sp015296. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Li Q., Altschuld R. A., Stokes B. T. Quantitation of intracellular free calcium in single adult cardiomyocytes by fura-2 fluorescence microscopy: calibration of fura-2 ratios. Biochem Biophys Res Commun. 1987 Aug 31;147(1):120–126. doi: 10.1016/s0006-291x(87)80095-5. [DOI] [PubMed] [Google Scholar]
  25. Moss R. L. Ca2+ regulation of mechanical properties of striated muscle. Mechanistic studies using extraction and replacement of regulatory proteins. Circ Res. 1992 May;70(5):865–884. doi: 10.1161/01.res.70.5.865. [DOI] [PubMed] [Google Scholar]
  26. Okazaki O., Suda N., Hongo K., Konishi M., Kurihara S. Modulation of Ca2+ transients and contractile properties by beta-adrenoceptor stimulation in ferret ventricular muscles. J Physiol. 1990 Apr;423:221–240. doi: 10.1113/jphysiol.1990.sp018019. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Rousseau E., Smith J. S., Meissner G. Ryanodine modifies conductance and gating behavior of single Ca2+ release channel. Am J Physiol. 1987 Sep;253(3 Pt 1):C364–C368. doi: 10.1152/ajpcell.1987.253.3.C364. [DOI] [PubMed] [Google Scholar]
  28. Schouten V. J., ter Keurs H. E. The force-frequency relationship in rat myocardium. The influence of muscle dimensions. Pflugers Arch. 1986 Jul;407(1):14–17. doi: 10.1007/BF00580714. [DOI] [PubMed] [Google Scholar]
  29. Spurgeon H. A., duBell W. H., Stern M. D., Sollott S. J., Ziman B. D., Silverman H. S., Capogrossi M. C., Talo A., Lakatta E. G. Cytosolic calcium and myofilaments in single rat cardiac myocytes achieve a dynamic equilibrium during twitch relaxation. J Physiol. 1992 Feb;447:83–102. doi: 10.1113/jphysiol.1992.sp018992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. 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]
  31. Yue D. T. Intracellular [Ca2+] related to rate of force development in twitch contraction of heart. Am J Physiol. 1987 Apr;252(4 Pt 2):H760–H770. doi: 10.1152/ajpheart.1987.252.4.H760. [DOI] [PubMed] [Google Scholar]
  32. 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]
  33. Zhao Y., Kawai M. The effect of the lattice spacing change on cross-bridge kinetics in chemically skinned rabbit psoas muscle fibers. II. Elementary steps affected by the spacing change. Biophys J. 1993 Jan;64(1):197–210. doi: 10.1016/S0006-3495(93)81357-2. [DOI] [PMC free article] [PubMed] [Google Scholar]

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