Skip to main content
Biophysical Journal logoLink to Biophysical Journal
. 1996 Jun;70(6):2527–2539. doi: 10.1016/S0006-3495(96)79824-7

Validity of the rapid buffering approximation near a point source of calcium ions.

G D Smith 1, J Wagner 1, J Keizer 1
PMCID: PMC1225234  PMID: 8744292

Abstract

In the presence of rapid buffers the full reaction-diffusion equations describing Ca2+ transport can be reduced using the rapid buffering approximation to a single transport equation for [Ca2+]. Here we simulate the full and reduced equations, exploring the conditions necessary for the validity of the rapid buffering approximation for an isolated Ca2+ channel or a cluster of channels. Using a point source and performing numerical simulations of different durations, we quantify the error of the rapid buffering approximation as a function of buffer and source parameters as well as the time and spatial scale set by the resolution of confocal microscopic measurements. We carry out simulations of Ca2+ "sparks" and "puffs," both with and without the indicator dye Ca2+ Green-1, and find that the rapid buffering approximation is excellent. These calculations also show that the traditional calculation of [Ca2+] from a fluorescence signal may grossly underestimate the true value of [Ca2+] near a source. Finally, we use the full model to simulate the transient Ca2+ domain near the pore of an open Ca2+ channel in a cell dialyzed with millimolar concentrations of 1,2-bis(2-aminophenoxy)ethane-N,N,N,N-tetraacetic acid or EGTA. In this regime, where the rapid buffering approximation is poor. Neher's equation for the steady-state Ca2+ profile is shown to be a reliable approximation adjacent to the pore.

Full text

PDF
2527

Selected References

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

  1. Allbritton N. L., Meyer T., Stryer L. Range of messenger action of calcium ion and inositol 1,4,5-trisphosphate. Science. 1992 Dec 11;258(5089):1812–1815. doi: 10.1126/science.1465619. [DOI] [PubMed] [Google Scholar]
  2. Baimbridge K. G., Celio M. R., Rogers J. H. Calcium-binding proteins in the nervous system. Trends Neurosci. 1992 Aug;15(8):303–308. doi: 10.1016/0166-2236(92)90081-i. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. Bezprozvanny I., Ehrlich B. E. Inositol (1,4,5)-trisphosphate (InsP3)-gated Ca channels from cerebellum: conduction properties for divalent cations and regulation by intraluminal calcium. J Gen Physiol. 1994 Nov;104(5):821–856. doi: 10.1085/jgp.104.5.821. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. 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]
  6. Blumenfeld H., Zablow L., Sabatini B. Evaluation of cellular mechanisms for modulation of calcium transients using a mathematical model of fura-2 Ca2+ imaging in Aplysia sensory neurons. Biophys J. 1992 Oct;63(4):1146–1164. doi: 10.1016/S0006-3495(92)81670-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. Cannell M. B., Cheng H., Lederer W. J. The control of calcium release in heart muscle. Science. 1995 May 19;268(5213):1045–1049. doi: 10.1126/science.7754384. [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. Eberhard M., Erne P. Calcium binding to fluorescent calcium indicators: calcium green, calcium orange and calcium crimson. Biochem Biophys Res Commun. 1991 Oct 15;180(1):209–215. doi: 10.1016/s0006-291x(05)81278-1. [DOI] [PubMed] [Google Scholar]
  11. Eckert R., Chad J. E. Inactivation of Ca channels. Prog Biophys Mol Biol. 1984;44(3):215–267. doi: 10.1016/0079-6107(84)90009-9. [DOI] [PubMed] [Google Scholar]
  12. Falke J. J., Drake S. K., Hazard A. L., Peersen O. B. Molecular tuning of ion binding to calcium signaling proteins. Q Rev Biophys. 1994 Aug;27(3):219–290. doi: 10.1017/s0033583500003012. [DOI] [PubMed] [Google Scholar]
  13. Fogelson A. L., Zucker R. S. Presynaptic calcium diffusion from various arrays of single channels. Implications for transmitter release and synaptic facilitation. Biophys J. 1985 Dec;48(6):1003–1017. doi: 10.1016/S0006-3495(85)83863-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. 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]
  15. Heinemann C., Chow R. H., Neher E., Zucker R. S. Kinetics of the secretory response in bovine chromaffin cells following flash photolysis of caged Ca2+. Biophys J. 1994 Dec;67(6):2546–2557. doi: 10.1016/S0006-3495(94)80744-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Heizmann C. W., Hunziker W. Intracellular calcium-binding proteins: more sites than insights. Trends Biochem Sci. 1991 Mar;16(3):98–103. doi: 10.1016/0968-0004(91)90041-s. [DOI] [PubMed] [Google Scholar]
  17. Jafri M. S., Keizer J. On the roles of Ca2+ diffusion, Ca2+ buffers, and the endoplasmic reticulum in IP3-induced Ca2+ waves. Biophys J. 1995 Nov;69(5):2139–2153. doi: 10.1016/S0006-3495(95)80088-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kao J. P. Practical aspects of measuring [Ca2+] with fluorescent indicators. Methods Cell Biol. 1994;40:155–181. doi: 10.1016/s0091-679x(08)61114-0. [DOI] [PubMed] [Google Scholar]
  19. Koster H. P., Hartog A., Van Os C. H., Bindels R. J. Calbindin-D28K facilitates cytosolic calcium diffusion without interfering with calcium signaling. Cell Calcium. 1995 Sep;18(3):187–196. doi: 10.1016/0143-4160(95)90063-2. [DOI] [PubMed] [Google Scholar]
  20. Llinás R., Sugimori M., Silver R. B. Microdomains of high calcium concentration in a presynaptic terminal. Science. 1992 May 1;256(5057):677–679. doi: 10.1126/science.1350109. [DOI] [PubMed] [Google Scholar]
  21. Neher E., Augustine G. J. Calcium gradients and buffers in bovine chromaffin cells. J Physiol. 1992 May;450:273–301. doi: 10.1113/jphysiol.1992.sp019127. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. 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]
  23. Parker I., Yao Y. Regenerative release of calcium from functionally discrete subcellular stores by inositol trisphosphate. Proc Biol Sci. 1991 Dec 23;246(1317):269–274. doi: 10.1098/rspb.1991.0154. [DOI] [PubMed] [Google Scholar]
  24. Pethig R., Kuhn M., Payne R., Adler E., Chen T. H., Jaffe L. F. On the dissociation constants of BAPTA-type calcium buffers. Cell Calcium. 1989 Oct;10(7):491–498. doi: 10.1016/0143-4160(89)90026-2. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. Roberts W. M., Jacobs R. A., Hudspeth A. J. Colocalization of ion channels involved in frequency selectivity and synaptic transmission at presynaptic active zones of hair cells. J Neurosci. 1990 Nov;10(11):3664–3684. doi: 10.1523/JNEUROSCI.10-11-03664.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Roberts W. M. Localization of calcium signals by a mobile calcium buffer in frog saccular hair cells. J Neurosci. 1994 May;14(5 Pt 2):3246–3262. doi: 10.1523/JNEUROSCI.14-05-03246.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Roberts W. M. Spatial calcium buffering in saccular hair cells. Nature. 1993 May 6;363(6424):74–76. doi: 10.1038/363074a0. [DOI] [PubMed] [Google Scholar]
  29. Sherman A., Keizer J., Rinzel J. Domain model for Ca2(+)-inactivation of Ca2+ channels at low channel density. Biophys J. 1990 Oct;58(4):985–995. doi: 10.1016/S0006-3495(90)82443-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Simon S. M., Llinás R. R. Compartmentalization of the submembrane calcium activity during calcium influx and its significance in transmitter release. Biophys J. 1985 Sep;48(3):485–498. doi: 10.1016/S0006-3495(85)83804-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Stern M. D. Buffering of calcium in the vicinity of a channel pore. Cell Calcium. 1992 Mar;13(3):183–192. doi: 10.1016/0143-4160(92)90046-u. [DOI] [PubMed] [Google Scholar]
  32. Tse A., Tse F. W., Hille B. Calcium homeostasis in identified rat gonadotrophs. J Physiol. 1994 Jun 15;477(Pt 3):511–525. doi: 10.1113/jphysiol.1994.sp020212. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Tsien R. Y. New calcium indicators and buffers with high selectivity against magnesium and protons: design, synthesis, and properties of prototype structures. Biochemistry. 1980 May 27;19(11):2396–2404. doi: 10.1021/bi00552a018. [DOI] [PubMed] [Google Scholar]
  34. 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]
  35. Wagner J., Keizer J. Effects of rapid buffers on Ca2+ diffusion and Ca2+ oscillations. Biophys J. 1994 Jul;67(1):447–456. doi: 10.1016/S0006-3495(94)80500-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Yao Y., Choi J., Parker I. Quantal puffs of intracellular Ca2+ evoked by inositol trisphosphate in Xenopus oocytes. J Physiol. 1995 Feb 1;482(Pt 3):533–553. doi: 10.1113/jphysiol.1995.sp020538. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Zhou Z., Neher E. Mobile and immobile calcium buffers in bovine adrenal chromaffin cells. J Physiol. 1993 Sep;469:245–273. doi: 10.1113/jphysiol.1993.sp019813. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Zweifach A., Lewis R. S. Rapid inactivation of depletion-activated calcium current (ICRAC) due to local calcium feedback. J Gen Physiol. 1995 Feb;105(2):209–226. doi: 10.1085/jgp.105.2.209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. de Leon M., Wang Y., Jones L., Perez-Reyes E., Wei X., Soong T. W., Snutch T. P., Yue D. T. Essential Ca(2+)-binding motif for Ca(2+)-sensitive inactivation of L-type Ca2+ channels. Science. 1995 Dec 1;270(5241):1502–1506. doi: 10.1126/science.270.5241.1502. [DOI] [PubMed] [Google Scholar]

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

RESOURCES