Skip to main content
Biophysical Journal logoLink to Biophysical Journal
. 2001 Jan;80(1):88–102. doi: 10.1016/S0006-3495(01)75997-8

Large currents generate cardiac Ca2+ sparks.

L T Izu 1, J R Mauban 1, C W Balke 1, W G Wier 1
PMCID: PMC1301216  PMID: 11159385

Abstract

Previous models of cardiac Ca2+ sparks have assumed that Ca2+ currents through the Ca2+ release units (CRUs) were approximately 1-2 pA, producing sparks with peak fluorescence ratio (F/F(0)) of approximately 2.0 and a full-width at half maximum (FWHM) of approximately 1 microm. Here, we present actual Ca2+ sparks with peak F/F(0) of >6 and a FWHM of approximately 2 microm, and a mathematical model of such sparks, the main feature of which is a much larger underlying Ca2+ current. Assuming infinite reaction rates and no endogenous buffers, we obtain a lower bound of approximately 11 pA needed to generate a Ca2+ spark with FWHM of 2 microm. Under realistic conditions, the CRU current must be approximately 20 pA to generate a 2- microm Ca2+)spark. For currents > or =5 pA, the computed spark amplitudes (F/F(0)) are large (approximately 6-12 depending on buffer model). We considered several factors that might produce sparks with FWHM approximately 2 microm without using large currents. Possible protein-dye interactions increased the FWHM slightly. Hypothetical Ca2+ "quarks" had little effect, as did blurring of sparks by the confocal microscope. A clusters of CRUs, each producing 10 pA simultaneously, can produce sparks with FWHM approximately 2 microm. We conclude that cardiac Ca2+ sparks are significantly larger in peak amplitude than previously thought, that such large Ca2+ sparks are consistent with the measured FWHM of approximately 2 microm, and that the underlying Ca2+ current is in the range of 10-20 pA.

Full Text

The Full Text of this article is available as a PDF (197.3 KB).

Selected References

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

  1. Backx P. H., de Tombe P. P., Van Deen J. H., Mulder B. J., ter Keurs H. E. A model of propagating calcium-induced calcium release mediated by calcium diffusion. J Gen Physiol. 1989 May;93(5):963–977. doi: 10.1085/jgp.93.5.963. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Balke C. W., Egan T. M., Wier W. G. Processes that remove calcium from the cytoplasm during excitation-contraction coupling in intact rat heart cells. J Physiol. 1994 Feb 1;474(3):447–462. doi: 10.1113/jphysiol.1994.sp020036. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Baylor S. M., Hollingworth S. Model of sarcomeric Ca2+ movements, including ATP Ca2+ binding and diffusion, during activation of frog skeletal muscle. J Gen Physiol. 1998 Sep;112(3):297–316. doi: 10.1085/jgp.112.3.297. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Berlin J. R., Bassani J. W., Bers D. M. Intrinsic cytosolic calcium buffering properties of single rat cardiac myocytes. Biophys J. 1994 Oct;67(4):1775–1787. doi: 10.1016/S0006-3495(94)80652-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Blatter L. A., Hüser J., Ríos E. Sarcoplasmic reticulum Ca2+ release flux underlying Ca2+ sparks in cardiac muscle. Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):4176–4181. doi: 10.1073/pnas.94.8.4176. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Blatter L. A., Wier W. G. Intracellular diffusion, binding, and compartmentalization of the fluorescent calcium indicators indo-1 and fura-2. Biophys J. 1990 Dec;58(6):1491–1499. doi: 10.1016/S0006-3495(90)82494-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cheng H., Lederer M. R., Lederer W. J., Cannell M. B. Calcium sparks and [Ca2+]i waves in cardiac myocytes. Am J Physiol. 1996 Jan;270(1 Pt 1):C148–C159. doi: 10.1152/ajpcell.1996.270.1.C148. [DOI] [PubMed] [Google Scholar]
  8. Cheng H., Lederer M. R., Xiao R. P., Gómez A. M., Zhou Y. Y., Ziman B., Spurgeon H., Lakatta E. G., Lederer W. J. Excitation-contraction coupling in heart: new insights from Ca2+ sparks. Cell Calcium. 1996 Aug;20(2):129–140. doi: 10.1016/s0143-4160(96)90102-5. [DOI] [PubMed] [Google Scholar]
  9. Cheng H., Lederer W. J., Cannell M. B. Calcium sparks: elementary events underlying excitation-contraction coupling in heart muscle. Science. 1993 Oct 29;262(5134):740–744. doi: 10.1126/science.8235594. [DOI] [PubMed] [Google Scholar]
  10. Cheng H., Song L. S., Shirokova N., González A., Lakatta E. G., Ríos E., Stern M. D. Amplitude distribution of calcium sparks in confocal images: theory and studies with an automatic detection method. Biophys J. 1999 Feb;76(2):606–617. doi: 10.1016/S0006-3495(99)77229-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Franzini-Armstrong C., Protasi F., Ramesh V. Shape, size, and distribution of Ca(2+) release units and couplons in skeletal and cardiac muscles. Biophys J. 1999 Sep;77(3):1528–1539. doi: 10.1016/S0006-3495(99)77000-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. González A., Kirsch W. G., Shirokova N., Pizarro G., Stern M. D., Ríos E. The spark and its ember: separately gated local components of Ca(2+) release in skeletal muscle. J Gen Physiol. 2000 Feb;115(2):139–158. doi: 10.1085/jgp.115.2.139. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Harkins A. B., Kurebayashi N., Baylor S. M. Resting myoplasmic free calcium in frog skeletal muscle fibers estimated with fluo-3. Biophys J. 1993 Aug;65(2):865–881. doi: 10.1016/S0006-3495(93)81112-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Izu L. T., Wier W. G., Balke C. W. Theoretical analysis of the Ca2+ spark amplitude distribution. Biophys J. 1998 Sep;75(3):1144–1162. doi: 10.1016/s0006-3495(98)74034-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Jiang Y. H., Klein M. G., Schneider M. F. Numerical simulation of Ca2+ "sparks" in skeletal muscle. Biophys J. 1999 Nov;77(5):2333–2357. doi: 10.1016/s0006-3495(99)77072-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lacampagne A., Ward C. W., Klein M. G., Schneider M. F. Time course of individual Ca2+ sparks in frog skeletal muscle recorded at high time resolution. J Gen Physiol. 1999 Feb;113(2):187–198. doi: 10.1085/jgp.113.2.187. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lipp P., Niggli E. Fundamental calcium release events revealed by two-photon excitation photolysis of caged calcium in Guinea-pig cardiac myocytes. J Physiol. 1998 May 1;508(Pt 3):801–809. doi: 10.1111/j.1469-7793.1998.801bp.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lipp P., Niggli E. Submicroscopic calcium signals as fundamental events of excitation--contraction coupling in guinea-pig cardiac myocytes. J Physiol. 1996 Apr 1;492(Pt 1):31–38. doi: 10.1113/jphysiol.1996.sp021286. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Lukyanenko V., Györke I., Györke S. Regulation of calcium release by calcium inside the sarcoplasmic reticulum in ventricular myocytes. Pflugers Arch. 1996 Oct;432(6):1047–1054. doi: 10.1007/s004240050233. [DOI] [PubMed] [Google Scholar]
  20. Lukyanenko V., Subramanian S., Gyorke I., Wiesner T. F., Gyorke S. The role of luminal Ca2+ in the generation of Ca2+ waves in rat ventricular myocytes. J Physiol. 1999 Jul 1;518(Pt 1):173–186. doi: 10.1111/j.1469-7793.1999.0173r.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. López-López J. R., Shacklock P. S., Balke C. W., Wier W. G. Local calcium transients triggered by single L-type calcium channel currents in cardiac cells. Science. 1995 May 19;268(5213):1042–1045. doi: 10.1126/science.7754383. [DOI] [PubMed] [Google Scholar]
  22. Parker I., Wier W. G. Variability in frequency and characteristics of Ca2+ sparks at different release sites in rat ventricular myocytes. J Physiol. 1997 Dec 1;505(Pt 2):337–344. doi: 10.1111/j.1469-7793.1997.337bb.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Parker I., Zang W. J., Wier W. G. Ca2+ sparks involving multiple Ca2+ release sites along Z-lines in rat heart cells. J Physiol. 1996 Nov 15;497(Pt 1):31–38. doi: 10.1113/jphysiol.1996.sp021747. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Rousseau E., Meissner G. Single cardiac sarcoplasmic reticulum Ca2+-release channel: activation by caffeine. Am J Physiol. 1989 Feb;256(2 Pt 2):H328–H333. doi: 10.1152/ajpheart.1989.256.2.H328. [DOI] [PubMed] [Google Scholar]
  25. Ríos E., Stern M. D., González A., Pizarro G., Shirokova N. Calcium release flux underlying Ca2+ sparks of frog skeletal muscle. J Gen Physiol. 1999 Jul;114(1):31–48. doi: 10.1085/jgp.114.1.31. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Shirokova N., Shirokov R., Rossi D., González A., Kirsch W. G., García J., Sorrentino V., Ríos E. Spatially segregated control of Ca2+ release in developing skeletal muscle of mice. J Physiol. 1999 Dec 1;521(Pt 2):483–495. doi: 10.1111/j.1469-7793.1999.00483.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Smith G. D., Keizer J. E., Stern M. D., Lederer W. J., Cheng H. A simple numerical model of calcium spark formation and detection in cardiac myocytes. Biophys J. 1998 Jul;75(1):15–32. doi: 10.1016/S0006-3495(98)77491-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Wier W. G., ter Keurs H. E., Marban E., Gao W. D., Balke C. W. Ca2+ 'sparks' and waves in intact ventricular muscle resolved by confocal imaging. Circ Res. 1997 Oct;81(4):462–469. doi: 10.1161/01.res.81.4.462. [DOI] [PubMed] [Google Scholar]
  29. Xiao R. P., Valdivia H. H., Bogdanov K., Valdivia C., Lakatta E. G., Cheng H. The immunophilin FK506-binding protein modulates Ca2+ release channel closure in rat heart. J Physiol. 1997 Apr 15;500(Pt 2):343–354. doi: 10.1113/jphysiol.1997.sp022025. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Biophysical Journal are provided here courtesy of The Biophysical Society

RESOURCES