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Dynamics of Calcium Fluxes in Nonexcitable Cells: Mathematical Modeling

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Abstract

Mathematical models simulating the dynamics of calcium redistribution (elicited by experimental interference with the pathways of calcium fluxes) in cellular compartments have been developed, based on a minimal scheme of the pathways of calcium fluxes in nonexcitable cells suspended in calcium-free medium. The models are consistent with available experimental data. All parameters are quantitatively related to the intrinsic properties of calcium adenosine triphosphatases (ATPases) and cellular membranes; there is no interdependence between the parameters. The models can be used as the basis for quantitative analysis and interpretation of experimental data. The activities of plasma membrane and sarcoendoplasmic reticulum calcium ATPases (PMCA and SERCAs) are governed by different mechanisms. PMCA is likely to undergo transitions from inactive to active to “dormant” (not identical to the initial) and back to inactive states, the mean duration of the cycle lasting for minutes or longer. The sequence of the transitions is initiated, presumably, by an increase in cytosolic calcium concentration. The transition of PMCA from inactive to active (at least at low rates of increase in cytosolic calcium concentration) is likely to be slower than that from active to dormant. SERCA, presumably, transits from inactive to active state in response to increases in calcium leakage from calcium stores. Whereas PMCA extrudes excess calcium (a definite quantity of it) in a short pulse, SERCA retakes calcium back into the stores permanently at a high rate. The models presented here may be the best means for the moment to quantitatively relate the dynamics of calcium fluxes in nonexcitable cells with known or putative properties of the mechanisms underlying activation of calcium ATPases.

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References

  • Beeler T.J., Jona I., Martonosi A. 1979. The effect of ionomycin on calcium fluxes in sarcoplasmic reticulum vesicles and liposomes. J. Biol. Chem. 254:6229–6231

    PubMed  CAS  Google Scholar 

  • Camello C., Lomax R., Petersen O.H., Tepikin A.V. 2002. Calcium leak from intracellular stores – the enigma of calcium signalling. Cell Calcium 32:355–361

    Article  PubMed  CAS  Google Scholar 

  • Caride A.J., Filoteo A.G., Penheiter A.R., Pászty K., Enyedi Á., Penniston J.T. 2001a. Delayed activation of the plasma membrane calcium pump by a sudden increase in Ca2+: Fast pumps reside in fast cells. Cell Calcium 30:49–57

    Article  CAS  Google Scholar 

  • Caride A.J., Penheiter A.R., Filoteo A.G., Bajzer Ž., Enyedi Á., Penniston J.T. 2001b. The plasma membrane calcium pump displays memory of past calcium spikes. Differences between isoforms 2b and 4b. J. Biol. Chem. 276:39797–39804

    Article  CAS  Google Scholar 

  • Cavallini L., Coassin M., Alexandre A. 1995. Two classes of agonist-sensitive Ca2+ stores in platelets, as identified by their differential sensitivity to 2,5-di-(tert-butyl)-1,4-benzohydroquinone and thapsigargin. Biochem. J. 310:449–452

    PubMed  CAS  Google Scholar 

  • Graupner M., Erler F., Meyer-Hermann M. 2005. A theory of plasma membrane calcium pump stimulation and activity. J. Biol. Phys. 31:183–206

    Article  CAS  Google Scholar 

  • Gunter T.E., Pfeiffer D.R. 1990. Mechanisms by which mitochondria transport calcium. Am. J. Physiol. 258:C755–C786

    PubMed  CAS  Google Scholar 

  • Hobbie R. K. 1997. Intermediate Physics for Medicine and Biology. Springer, New York

    Google Scholar 

  • Juška A., Redondo P.C., Rosado J.A., Salido G.M. 2005. Dynamics of calcium fluxes in human platelets assessed in calcium-free medium. Biochem. Biophys. Res. Commun. 334:779–786

    Article  PubMed  Google Scholar 

  • Kauffman R.F., Taylor R.W., Pfeiffer D.R. 1980. Cation transport and specificity of ionomycin. Comparison with ionophore A23187 in rat liver mitochondria. J. Biol. Chem. 255:2735–2739

    PubMed  CAS  Google Scholar 

  • Nicholls D.G., Chalmers S. 2004. The integration of mitochondrial calcium transport and storage. J. Bioenerg. Biomembr. 36:277–281

    Article  PubMed  CAS  Google Scholar 

  • Osborn K.D., Zaidi A., Mandal A., Urbauer R.J., Johnson C.K. 2004. Single-molecule dynamics of the calcium-dependent activation of plasma-membrane Ca2+-ATPase by calmodulin. Biophys. J. 87:1892–1899

    Article  PubMed  CAS  Google Scholar 

  • Papp B., Enyedi Á., Kovacs T., Sarkadi B., Wuytack F., Thastrup O., Gardos G., Bredoux R., Levy-Toledano S., Enouf J. 1991. Demonstration of two forms of calcium pumps by thapsigargin inhibition and radioimmunoblotting in platelet membrane vesicles. J. Biol. Chem. 266:14593–14596

    PubMed  CAS  Google Scholar 

  • Parekh A.B. 2003. Mitochondrial regulation of intracellular Ca2+ signaling: More than just simple Ca2+ buffers. News Physiol. Sci. 18:252–256

    PubMed  CAS  Google Scholar 

  • Paul, B.Z.S., Daniel, J.L., Kunapuli, S.P. 1999. Platelet shape change is mediated by both calcium-dependent and -independent signaling pathways. J. Biol. Chem. 274:28293–28300

    Google Scholar 

  • Penheiter A.R., Bajzer Ž., Filoteo A.G., Thorogate R., Török K., Caride A.J. 2003. A model for the activation of plasma membrane calcium pump isoform 4b by calmodulin. Biochemistry 42:12115–12124

    Article  PubMed  CAS  Google Scholar 

  • Penniston J.T., Enyedi Á. 1998. Modulation of the plasma membrane Ca2+ pump. J. Membr. Biol. 165:101–109

    Article  PubMed  CAS  Google Scholar 

  • Pinton P., Pozzan T., Rizzuto R. 1998. The Golgi apparatus is an inositol 1,4,5-trisphosphate-sensitive Ca2+ store, with functional properties distinct from those of the endoplasmic reticulum. EMBO J. 17:5298–5308

    Article  PubMed  CAS  Google Scholar 

  • Pizzo P., Fasolato C., Pozzan T. 1997. Dynamic properties of an inositol 1,4,5-trisphosphate- and thapsigargin-insensitive calcium pool in mammalian cell lines. J. Cell Biol. 136:355–366

    Article  PubMed  CAS  Google Scholar 

  • Pozzan T., Rizzuto R., Volpe P., Meldolesi J. 1994. Molecular and cellular physiology of intracellular calcium stores. Physiol. Rev. 74:595–636

    PubMed  CAS  Google Scholar 

  • Rink T.J., Sage S.O. 1990. Calcium signaling in human platelets. Annu. Rev. Physiol. 52:431–449

    Article  PubMed  CAS  Google Scholar 

  • Rizzuto R., Pozzan T., Carafoli E. 2002. Ca2+ on the move: Ways and means to translate a multifarious signal. Trends Pharmacol. Sci. 23:348–350

    Article  PubMed  CAS  Google Scholar 

  • Rosado J.A., Sage S.O. 2000. Regulation of plasma membrane Ca2+-ATPase by small GTPases and phosphoinositides in human platelets. J. Biol. Chem. 275:19529–19535

    Article  PubMed  CAS  Google Scholar 

  • Saavedra, F.R., Redondo, P.C., Herna´ndez-Cruz, J.M., Salido, G.M., Pariente, J.A., Rosado, J.A. 2004. Store-operated CA2+ entry and tyrosine kinase pp60src hyperactivity are modulated by hyperglycemia in platelets from patients with non insulin-dependent diabetes mellitus. Arch. Biochem. Biophys. 432:261–268

    Article  PubMed  CAS  Google Scholar 

  • Stokes D.L., Green N.M. 2003. Structure and function of the calcium pump. Annu. Rev. Biophys. Biomol. Struct. 32:445–468

    Article  PubMed  CAS  Google Scholar 

  • Wang D.N. 1994. Band 3 protein: Structure, flexibility and function. FEBS Lett. 346:26–31

    Article  PubMed  CAS  Google Scholar 

  • Young H.S., Stokes D.L. 2004. The mechanics of calcium transport. J. Membr. Biol. 198:55–63

    PubMed  CAS  Google Scholar 

  • Żylińska L., Soszyński M. 2000. Plasma membrane Ca2+-ATPase in excitable and nonexcitable cells. Acta Biochim. Pol. 47:529–539

    PubMed  Google Scholar 

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Acknowledgment

I thank Prof. G. M. Salido, Dr. J. A. Rosado and Dr. P. C. Redondo for their comments on the manuscript and valuable suggestions, as well as PhD student T. Rekašius for his help with the probabilistic interpretations. Special thanks to my students D. Mažeika and R. Stupak for their interest and curiosity: Figure 1B , scheme 7 and equation 10 emerged due to attempts to best answer their questions. I also thank the reviewers for their comments and criticism, which helped to improve the paper.

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  1. Vilniaus Gedimino technikos universitetas, Saulėtekio al. 11, 10223, Vilnius-40, Lithuania

    Alfonsas Juška

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  1. Alfonsas Juška
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Correspondence to Alfonsas Juška.

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Juška, A. Dynamics of Calcium Fluxes in Nonexcitable Cells: Mathematical Modeling. J Membrane Biol 211, 89–99 (2006). https://doi.org/10.1007/s00232-005-7019-3

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  • DOI: https://doi.org/10.1007/s00232-005-7019-3

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