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. 1998 Jan;74(1):153–174. doi: 10.1016/S0006-3495(98)77776-8

Calcium concentration and movement in the ventricular cardiac cell during an excitation-contraction cycle.

A Peskoff 1, G A Langer 1
PMCID: PMC1299371  PMID: 9449319

Abstract

This paper extends the model for Ca movement in the cardiac ventricular cell from the diadic cleft space to the entire sarcomere. The model predicts the following: 1) Shortly after SR release there is a [Ca] gradient >3 orders of magnitude from cleft center to M-line which, 50 ms after release, is still >30. Outside the cleft, 40 ms after cessation of release, the axial gradient from Z to M-line is >3. 2) At the end of SR release, >50% of the total Ca released is bound to low-affinity inner sarcolemmal phospholipid binding sites within the cleft. 3) Halving the SR release almost doubles the fraction of release removed from the cell via Na/Ca exchange and reduces average sarcomeric free [Ca] by 70%. 4) Adding 100 microM fluo-3, which doubles the buffering capacity of the cytoplasm, reduces peak average sarcomeric [Ca] by >50% and increases the initial half-time for [Ca] decrease by approximately twofold. 5) A typical Ca "spark" can be generated by an SR release 20% of maximum (4 x 10(-20) moles) over 2 ms. Fluo-3 (100 microM) significantly "shrinks" the spark. 6) The "spark" is a consequence of elementary events within the diadic cleft space. For example, removal of cleft binding sites would cause average sarcomeric Ca to increase by >10 fold, fall 10 times more rapidly, decrease latency for appearance of the spark by >20 times, and reduce spark duration by 85%. 7) Dividing SR Ca release between cleft and corbular SR produces a secondary [Ca] peak and a "flattening" of the sarcomeric [Ca] transient. These changes probably could not be resolved with current confocal microscopic techniques.

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Selected References

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  1. Bassani J. W., Bassani R. A., Bers D. M. Relaxation in rabbit and rat cardiac cells: species-dependent differences in cellular mechanisms. J Physiol. 1994 Apr 15;476(2):279–293. doi: 10.1113/jphysiol.1994.sp020130. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Cannell M. B., Cheng H., Lederer W. J. Spatial non-uniformities in [Ca2+]i during excitation-contraction coupling in cardiac myocytes. Biophys J. 1994 Nov;67(5):1942–1956. doi: 10.1016/S0006-3495(94)80677-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  4. 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]
  5. Dolber P. C., Sommer J. R. Corbular sarcoplasmic reticulum of rabbit cardiac muscle. J Ultrastruct Res. 1984 May;87(2):190–196. doi: 10.1016/s0022-5320(84)80078-7. [DOI] [PubMed] [Google Scholar]
  6. Escobar A. L., Cifuentes F., Vergara J. L. Detection of Ca(2+)-transients elicited by flash photolysis of DM-nitrophen with a fast calcium indicator. FEBS Lett. 1995 May 15;364(3):335–338. doi: 10.1016/0014-5793(95)00425-9. [DOI] [PubMed] [Google Scholar]
  7. Fabiato A. Time and calcium dependence of activation and inactivation of calcium-induced release of calcium from the sarcoplasmic reticulum of a skinned canine cardiac Purkinje cell. J Gen Physiol. 1985 Feb;85(2):247–289. doi: 10.1085/jgp.85.2.247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Frank J. S., Mottino G., Reid D., Molday R. S., Philipson K. D. Distribution of the Na(+)-Ca2+ exchange protein in mammalian cardiac myocytes: an immunofluorescence and immunocolloidal gold-labeling study. J Cell Biol. 1992 Apr;117(2):337–345. doi: 10.1083/jcb.117.2.337. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Isenberg G., Etter E. F., Wendt-Gallitelli M. F., Schiefer A., Carrington W. A., Tuft R. A., Fay F. S. Intrasarcomere [Ca2+] gradients in ventricular myocytes revealed by high speed digital imaging microscopy. Proc Natl Acad Sci U S A. 1996 May 28;93(11):5413–5418. doi: 10.1073/pnas.93.11.5413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Jorgensen A. O., Shen A. C., Campbell K. P. Ultrastructural localization of calsequestrin in adult rat atrial and ventricular muscle cells. J Cell Biol. 1985 Jul;101(1):257–268. doi: 10.1083/jcb.101.1.257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kao J. P., Harootunian A. T., Tsien R. Y. Photochemically generated cytosolic calcium pulses and their detection by fluo-3. J Biol Chem. 1989 May 15;264(14):8179–8184. [PubMed] [Google Scholar]
  12. Langer G. A., Peskoff A. Calcium concentration and movement in the diadic cleft space of the cardiac ventricular cell. Biophys J. 1996 Mar;70(3):1169–1182. doi: 10.1016/S0006-3495(96)79677-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Levitsky D. O., Benevolensky D. S., Levchenko T. S., Smirnov V. N., Chazov E. I. Calcium-binding rate and capacity of cardiac sarcoplasmic reticulum. J Mol Cell Cardiol. 1981 Sep;13(9):785–796. doi: 10.1016/0022-2828(81)90236-4. [DOI] [PubMed] [Google Scholar]
  14. Luo C. H., Rudy Y. A dynamic model of the cardiac ventricular action potential. I. Simulations of ionic currents and concentration changes. Circ Res. 1994 Jun;74(6):1071–1096. doi: 10.1161/01.res.74.6.1071. [DOI] [PubMed] [Google Scholar]
  15. Matsuoka S., Hilgemann D. W. Steady-state and dynamic properties of cardiac sodium-calcium exchange. Ion and voltage dependencies of the transport cycle. J Gen Physiol. 1992 Dec;100(6):963–1001. doi: 10.1085/jgp.100.6.963. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Minta A., Kao J. P., Tsien R. Y. Fluorescent indicators for cytosolic calcium based on rhodamine and fluorescein chromophores. J Biol Chem. 1989 May 15;264(14):8171–8178. [PubMed] [Google Scholar]
  17. Nowycky M. C., Pinter M. J. Time courses of calcium and calcium-bound buffers following calcium influx in a model cell. Biophys J. 1993 Jan;64(1):77–91. doi: 10.1016/S0006-3495(93)81342-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Peskoff A., Post J. A., Langer G. A. Sarcolemmal calcium binding sites in heart: II. Mathematical model for diffusion of calcium released from the sarcoplasmic reticulum into the diadic region. J Membr Biol. 1992 Jul;129(1):59–69. doi: 10.1007/BF00232055. [DOI] [PubMed] [Google Scholar]
  19. Post J. A., Langer G. A., Op den Kamp J. A., Verkleij A. J. Phospholipid asymmetry in cardiac sarcolemma. Analysis of intact cells and 'gas-dissected' membranes. Biochim Biophys Acta. 1988 Aug 18;943(2):256–266. doi: 10.1016/0005-2736(88)90557-3. [DOI] [PubMed] [Google Scholar]
  20. Post J. A., Langer G. A. Sarcolemmal calcium binding sites in heart: I. Molecular origin in "gas-dissected" sarcolemma. J Membr Biol. 1992 Jul;129(1):49–57. doi: 10.1007/BF00232054. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. Radermacher M., Rao V., Grassucci R., Frank J., Timerman A. P., Fleischer S., Wagenknecht T. Cryo-electron microscopy and three-dimensional reconstruction of the calcium release channel/ryanodine receptor from skeletal muscle. J Cell Biol. 1994 Oct;127(2):411–423. doi: 10.1083/jcb.127.2.411. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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]
  24. Rousseau E., Smith J. S., Henderson J. S., Meissner G. Single channel and 45Ca2+ flux measurements of the cardiac sarcoplasmic reticulum calcium channel. Biophys J. 1986 Nov;50(5):1009–1014. doi: 10.1016/S0006-3495(86)83543-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Santana L. F., Cheng H., Gómez A. M., Cannell M. B., Lederer W. J. Relation between the sarcolemmal Ca2+ current and Ca2+ sparks and local control theories for cardiac excitation-contraction coupling. Circ Res. 1996 Jan;78(1):166–171. doi: 10.1161/01.res.78.1.166. [DOI] [PubMed] [Google Scholar]
  26. Shacklock P. S., Wier W. G., Balke C. W. Local Ca2+ transients (Ca2+ sparks) originate at transverse tubules in rat heart cells. J Physiol. 1995 Sep 15;487(Pt 3):601–608. doi: 10.1113/jphysiol.1995.sp020903. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Sipido K. R., Wier W. G. Flux of Ca2+ across the sarcoplasmic reticulum of guinea-pig cardiac cells during excitation-contraction coupling. J Physiol. 1991 Apr;435:605–630. doi: 10.1113/jphysiol.1991.sp018528. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Smith G. D., Wagner J., Keizer J. Validity of the rapid buffering approximation near a point source of calcium ions. Biophys J. 1996 Jun;70(6):2527–2539. doi: 10.1016/S0006-3495(96)79824-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Spurgeon H. A., Stern M. D., Baartz G., Raffaeli S., Hansford R. G., Talo A., Lakatta E. G., Capogrossi M. C. Simultaneous measurement of Ca2+, contraction, and potential in cardiac myocytes. Am J Physiol. 1990 Feb;258(2 Pt 2):H574–H586. doi: 10.1152/ajpheart.1990.258.2.H574. [DOI] [PubMed] [Google Scholar]
  30. Takamatsu T., Wier W. G. Calcium waves in mammalian heart: quantification of origin, magnitude, waveform, and velocity. FASEB J. 1990 Mar;4(5):1519–1525. doi: 10.1096/fasebj.4.5.2307330. [DOI] [PubMed] [Google Scholar]
  31. Wang S. Y., Peskoff A., Langer G. A. Inner sarcolemmal leaflet Ca(2+) binding: its role in cardiac Na/Ca exchange. Biophys J. 1996 May;70(5):2266–2274. doi: 10.1016/S0006-3495(96)79792-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Wibo M., Bravo G., Godfraind T. Postnatal maturation of excitation-contraction coupling in rat ventricle in relation to the subcellular localization and surface density of 1,4-dihydropyridine and ryanodine receptors. Circ Res. 1991 Mar;68(3):662–673. doi: 10.1161/01.res.68.3.662. [DOI] [PubMed] [Google Scholar]
  33. 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]

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