Summary
An increase in the intracellular free calcium concentration, [Ca2+]i, initiates contractile activation in the heart. Until recently, the changes in [Ca2+]i during the cardiac cycle (the “Ca2+ transients”) had eluded measurement. Here I describe the use of gated nuclear magnetic resonance (NMR) spectroscopy to achieve direct quantitation of the cyclical changes in [Ca2+]i that underlie mechanics in perfused ferret hearts loaded with-the fluorinated Ca2+ indicator 5F-BAPTA. [Ca2+]i increased from approximately 200 nM in diastole to 750 nM or higher in early systole. In this preparation, the effects of changing coronary arterial flow on [Ca2+]i can be investigated simultaneously with measurements of high-energy phosphate concentrations by 31P-NMR. When hypoperfusion is induced such that the pressure generated by contraction falls without metabolic evidence of ischemia (“Gregg’s phenomenon”), a decrease in the amplitude of Ca2+ transients underlies the observed fall in pressure. This down-regulation of Ca2+ transients constitutes the cellular basis for Gregg’s phenomenon, and serves to decrease energy demand during low-flow ischemia.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
Similar content being viewed by others
References
Blinks JR, Wier WG, Hess P, Prendergast FG (1984) Measurement of Ca2+ concentrations in living cells. Prog Biophys Mol Biol 40: 1–114
Smith GA, Hesketh RT, Metcalfe JC, Feeney J, Morris PG (1983) Intracellular calcium measurements by 19F NMR of fluorine-labelled chelators. Proc Natl Acad Sci USA 80: 7178–7182
Metcalfe JC, Hesketh TR, Smith GA (1985) Free cytosolic Ca2+ measurements with fluorine labelled indicators using 19F NMR. Cell Calcium 6: 183–195
Marban E, Kitakaze M, Kusuoka H, Porterfield JK, Yue DT, Chacko VP (1987) Intracellular free calcium concentration measured with 19F NMR spectroscopy in intact ferret hearts. Proc Natl Acad Sci USA 84: 6005–6009
Steenbergen C, Murphy E, Levy L, London RE (1987) Elevation in cytosolic free calcium concentration early in myocardial ischemia in perfused rat heart. Circ Res 60: 700–707
Marban E, Kitakaze M, Chacko VP, Pike MM (1988) Ca2+ transients in perfused ferret hearts revealed by 19F NMR spectroscopy. Circ Res
Kusuoka H, Weisfeldt ML, Jacobus WE, Zweier J, Marban E (1986) Mechanism of early contractile failure during hypoxia in intact ferret heart: evidence for modulation of maximal Ca2+-activated force by inorganic phosphate. Circ Res 59: 270–282
Morris GM, Allen DG, Orchard CL (1984) High-time-resolution 31P NMR studies of the perfused ferret heart. Advances in Myocardiology 5: 27–38
Fossel ET, Morgan HE, Ingwall JS (1980) Measurement of changes in high-energy phosphates in the cardiac cycle by using gated 31P nuclear magnetic resonance. Proc Natl Acad Sci USA 77: 3654–3658
Wikman-Coffelt J, Sievers R, Coffelt RJ, Parmley WW (1983) The cardiac cycle: regulation and energy oscillations. Am J Physiol 245, H354
Kusuoka H, Inoue M, Tsuneoka Y, Watari H, Hori M, Abe H (1985) Augmented energy consumption during early systole as a mechanism of cyclical changes in high-energy phosphates in myocardium assessed by phosphorus nuclear magnetic resonance. Jpn Circ J 49: 1099–1107
Yue DT (1987) Intracellular [Ca2+] related to rate of force development in twitch contraction of heart. Am J Physiol 252: H760-H770
Wier WG, Yue DT (1986) Intracellular [Ca2+] transients underlying the short-term force-interval relationship in ferret ventricular myocardium. J Physiol (Lond) 376: 507–530
Flaherty JT, Weisfeldt ML, Bulkley BH, Gardner TJ, Gott VL, Jacobus WE (1982) Mechanisms of ischemic myocardial cell damage assessed by 31-phosphorus nuclear magnetic resonance. Circulation 65: 561–571
Jacobus WE, Pores IH, Lucas SK, Kallman CH, Weisfeldt ML, Flaherty JT (1982) The role of intracellular pH in the control of normal and ischemic myocardial contractility. In: Nuccitelli R, Deamer DW (eds) Intracellular pH: its measurement, regulation and utilization in cellular function, Alan R Liss, New York, pp 537–565
Feigl E (1983) Coronary physiology. Physiol Rev 63: 1–205
Braunwald E, Rutherford JD (1986) Reversible ischemic left ventricular dysfunction: evidence for the “hibernating myocardium”. J Am Coll Cardiol 8: 1467–1470
Lattanzio FA, Pressman BC (1986) Alterations in intracellular calcium activity and contractility of isolated perfused rabbit hearts by ionophore and adrenergic agents. Biochem Biophys Res Commun 139: 816–821
Lee HC, Smith N, Mohabir R, Clusin WT (1987) Cytosolic calcium transients from the beating mammalian heart. Proc Natl Acad Sci USA 84: 7793–7797
Suga H, Hisano R, Goto Y, Yamada O, Igarashi Y (1983) Effect of positive inotropic agents on the relation between oxygen consumption and systolic pressure-volume area in canine left ventricle. Circ Res 53: 306–318
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1989 Springer-Verlag Tokyo
About this chapter
Cite this chapter
Marban, E. (1989). Ca2+ Transients in Perfused Hearts: Fundamental Properties of the Chemical Signals Underlying Ventricular Mechanics. In: Hori, M., Suga, H., Baan, J., Yellin, E.L. (eds) Cardiac Mechanics and Function in the Normal and Diseased Heart. Springer, Tokyo. https://doi.org/10.1007/978-4-431-67957-8_1
Download citation
DOI: https://doi.org/10.1007/978-4-431-67957-8_1
Publisher Name: Springer, Tokyo
Print ISBN: 978-4-431-68020-8
Online ISBN: 978-4-431-67957-8
eBook Packages: Springer Book Archive