Skip to main content
Biophysical Journal logoLink to Biophysical Journal
. 2001 Jan;80(1):169–183. doi: 10.1016/S0006-3495(01)76005-5

A preferred amplitude of calcium sparks in skeletal muscle.

E Ríos 1, N Shirokova 1, W G Kirsch 1, G Pizarro 1, M D Stern 1, H Cheng 1, A González 1
PMCID: PMC1301224  PMID: 11159393

Abstract

In skeletal and cardiac muscle, calcium release from the sarcoplasmic reticulum, leading to contraction, often results in calcium sparks. Because sparks are recorded by confocal microscopy in line-scanning mode, their measured amplitude depends on their true amplitude and the position of the spark relative to the scanned line. We present a method to derive from measured amplitude histograms the actual distribution of spark amplitudes. The method worked well when tested on simulated distributions of experimental sparks. Applied to massive numbers of sparks imaged in frog skeletal muscle under voltage clamp in reference conditions, the method yielded either a decaying amplitude distribution (6 cells) or one with a central mode (5 cells). Caffeine at 0.5 or 1 mM reversibly enhanced this mode (5 cells) or induced its appearance (4 cells). The occurrence of a mode in the amplitude distribution was highly correlated with the presence of a mode in the distribution of spark rise times or in the joint distribution of rise times and spatial widths. If sparks were produced by individual Markovian release channels evolving reversibly, they should not have a preferred rise time or amplitude. Channel groups, instead, could cooperate allosterically or through their calcium sensitivity, and give rise to a stereotyped amplitude in their collective spark.

Full Text

The Full Text of this article is available as a PDF (518.2 KB).

Selected References

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

  1. 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]
  2. Bridge J. H., Ershler P. R., Cannell M. B. Properties of Ca2+ sparks evoked by action potentials in mouse ventricular myocytes. J Physiol. 1999 Jul 15;518(Pt 2):469–478. doi: 10.1111/j.1469-7793.1999.0469p.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brum G., González A., Rengifo J., Shirokova N., Ríos E. Fast imaging in two dimensions resolves extensive sources of Ca2+ sparks in frog skeletal muscle. J Physiol. 2000 Nov 1;528(Pt 3):419–433. doi: 10.1111/j.1469-7793.2000.00419.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cannell M. B., Soeller C. Mechanisms underlying calcium sparks in cardiac muscle. J Gen Physiol. 1999 Mar;113(3):373–376. doi: 10.1085/jgp.113.3.373. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chen T. Y., Miller C. Nonequilibrium gating and voltage dependence of the ClC-0 Cl- channel. J Gen Physiol. 1996 Oct;108(4):237–250. doi: 10.1085/jgp.108.4.237. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. 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]
  8. Endo M., Tanaka M., Ogawa Y. Calcium induced release of calcium from the sarcoplasmic reticulum of skinned skeletal muscle fibres. Nature. 1970 Oct 3;228(5266):34–36. doi: 10.1038/228034a0. [DOI] [PubMed] [Google Scholar]
  9. Franzini-Armstrong C., Jorgensen A. O. Structure and development of E-C coupling units in skeletal muscle. Annu Rev Physiol. 1994;56:509–534. doi: 10.1146/annurev.ph.56.030194.002453. [DOI] [PubMed] [Google Scholar]
  10. González A., Kirsch W. G., Shirokova N., Pizarro G., Brum G., Pessah I. N., Stern M. D., Cheng H., Ríos E. Involvement of multiple intracellular release channels in calcium sparks of skeletal muscle. Proc Natl Acad Sci U S A. 2000 Apr 11;97(8):4380–4385. doi: 10.1073/pnas.070056497. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. 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]
  12. Gration K. A., Lambert J. J., Ramsey R. L., Rand R. P., Usherwood P. N. Closure of membrane channels gated by glutamate receptors may be a two-step process. Nature. 1982 Feb 18;295(5850):599–603. doi: 10.1038/295599a0. [DOI] [PubMed] [Google Scholar]
  13. Herrmann-Frank A., Lüttgau H. C., Stephenson D. G. Caffeine and excitation-contraction coupling in skeletal muscle: a stimulating story. J Muscle Res Cell Motil. 1999 Feb;20(2):223–237. doi: 10.1023/a:1005496708505. [DOI] [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. Klein M. G., Cheng H., Santana L. F., Jiang Y. H., Lederer W. J., Schneider M. F. Two mechanisms of quantized calcium release in skeletal muscle. Nature. 1996 Feb 1;379(6564):455–458. doi: 10.1038/379455a0. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. 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]
  19. Nelson M. T., Cheng H., Rubart M., Santana L. F., Bonev A. D., Knot H. J., Lederer W. J. Relaxation of arterial smooth muscle by calcium sparks. Science. 1995 Oct 27;270(5236):633–637. doi: 10.1126/science.270.5236.633. [DOI] [PubMed] [Google Scholar]
  20. Pratusevich V. R., Balke C. W. Factors shaping the confocal image of the calcium spark in cardiac muscle cells. Biophys J. 1996 Dec;71(6):2942–2957. doi: 10.1016/S0006-3495(96)79525-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Ríos E., Karhanek M., Ma J., González A. An allosteric model of the molecular interactions of excitation-contraction coupling in skeletal muscle. J Gen Physiol. 1993 Sep;102(3):449–481. doi: 10.1085/jgp.102.3.449. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. 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]
  23. Schneggenburger R., Ascher P. Coupling of permeation and gating in an NMDA-channel pore mutant. Neuron. 1997 Jan;18(1):167–177. doi: 10.1016/s0896-6273(01)80055-6. [DOI] [PubMed] [Google Scholar]
  24. Schneider M. F. Ca2+ sparks in frog skeletal muscle: generation by one, some, or many SR Ca2+ release channels? J Gen Physiol. 1999 Mar;113(3):365–372. doi: 10.1085/jgp.113.3.365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Sham J. S., Song L. S., Chen Y., Deng L. H., Stern M. D., Lakatta E. G., Cheng H. Termination of Ca2+ release by a local inactivation of ryanodine receptors in cardiac myocytes. Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):15096–15101. doi: 10.1073/pnas.95.25.15096. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Shirokova N., González A., Kirsch W. G., Ríos E., Pizarro G., Stern M. D., Cheng H. Calcium sparks: release packets of uncertain origin and fundamental role. J Gen Physiol. 1999 Mar;113(3):377–384. doi: 10.1085/jgp.113.3.377. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Shirokova N., Ríos E. Small event Ca2+ release: a probable precursor of Ca2+ sparks in frog skeletal muscle. J Physiol. 1997 Jul 1;502(Pt 1):3–11. doi: 10.1111/j.1469-7793.1997.003bl.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. 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]
  29. Stern M. D., Pizarro G., Ríos E. Local control model of excitation-contraction coupling in skeletal muscle. J Gen Physiol. 1997 Oct;110(4):415–440. doi: 10.1085/jgp.110.4.415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Tripathy A., Meissner G. Sarcoplasmic reticulum lumenal Ca2+ has access to cytosolic activation and inactivation sites of skeletal muscle Ca2+ release channel. Biophys J. 1996 Jun;70(6):2600–2615. doi: 10.1016/S0006-3495(96)79831-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Tsugorka A., Ríos E., Blatter L. A. Imaging elementary events of calcium release in skeletal muscle cells. Science. 1995 Sep 22;269(5231):1723–1726. doi: 10.1126/science.7569901. [DOI] [PubMed] [Google Scholar]
  32. Xu L., Meissner G. Regulation of cardiac muscle Ca2+ release channel by sarcoplasmic reticulum lumenal Ca2+. Biophys J. 1998 Nov;75(5):2302–2312. doi: 10.1016/S0006-3495(98)77674-X. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES