Log in

Mathematical Modeling of Calcium Oscillatory Patterns in a Neuron

  • Original research article
  • Published:
Interdisciplinary Sciences: Computational Life Sciences Aims and scope Submit manuscript

Abstract

Calcium oscillations are an imperative mode of signaling phenomenon. These oscillations are due to the active interactions taking place between some of the parameters like voltage gated calcium channels (VGCC), sodium calcium exchanger (NCX), calcium binding buffers, endoplasmic reticulum (ER) and mitochondria. The present paper focuses on the problem of higher level of calcium concentration in neurons which may further result into Alzheimer’s Disease (AD). For this, a three-dimensional mathematical model having a system of differential equations depicting the changes in cytosolic calcium (in presence of buffers, VGCC and NCX), ER calcium and mitochondrial calcium, is formulated. A three-dimensional neuronal structure is targeted as the domain which is further discussed and solved using finite element technique in Comsol Multiphysics 5.4. Apposite boundary conditions matching well with the in-situ conditions are assumed. The obtained results clearly show the significance of the lower amount of the buffer and higher calcium mediated activities of VGCC, NCX, ER and mitochondria on calcium profile. These changes may lead to AD. To transit from AD condition to normal, exogenous buffers are added to check their significance. The results thus show that the replenishment of buffer may balance the amount of cell calcium and hence can affect positively on Alzheimer’s affected cells.

Graphic abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (United Kingdom)

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Augustine GJ, Santamaria F, Tanaka K (2003) Local calcium signaling in neurons. Neuron 40:331–346. https://doi.org/10.1016/s0896-6273(03)00639-1

    Article  CAS  PubMed  Google Scholar 

  2. Benarroch EE (2010) Neuronal voltage-gated calcium channels: brief overview of their function and clinical implications in neurology. Neurology 74:1310–1315. https://doi.org/10.1212/WNL.0b013e3181da364b

    Article  PubMed  Google Scholar 

  3. Berridge MJ (1998) Neuronal calcium signaling. Neuron 21:13–26. https://doi.org/10.1016/s0896-6273(00)80510-3

    Article  CAS  PubMed  Google Scholar 

  4. Bertram R, Tabak J, Teka W, Vo T, Wechselberger M, Kirk V, Sneyd J (2015) Math Anal Complex Cellular Activity. https://doi.org/10.1007/978-3-319-18114-1

    Article  Google Scholar 

  5. Bezprozvanny I (2011) Calcium signalling and neurodegenerative diseases. Trends Mol Med 15(3):89–100. https://doi.org/10.1016/j.molmed.2009.01.001.Calcium

    Article  Google Scholar 

  6. Blaustein MP, Lederer WJ (1999) Sodium / calcium exchange : its physiological implications. Physiol Rev 79(3):763–854. https://doi.org/10.1152/physrev.1999.79.3.763

    Article  CAS  PubMed  Google Scholar 

  7. Colvin RA, Bennett JW, Colvin SL (1991) Na+-Ca2+ exchange activity is increased in Alzheimer’s Disease brain tissues. Ann N Y Acad Sci 639:325–327. https://doi.org/10.1111/j.1749-6632.1991.tb17320.x

    Article  CAS  PubMed  Google Scholar 

  8. Dave DD, Jha BK (2018) Analytically depicting the calcium diffusion for Alzheimer’s affected cell. Int J Biomath 11(6), https://doi.org/10.1142/S1793524518500882

  9. Dave DD, Jha BK (2018) Delineation of calcium diffusion in alzheimeric brain. J Mech Med Biol 18(2):1–15. https://doi.org/10.1142/S0219519418500288

    Article  CAS  Google Scholar 

  10. Dave DD, Jha BK (2020) 3D mathematical modeling of calcium signaling in Alzheimer’s disease. Netw Modeling Anal Health Inform Bioinform 3:1–10. https://doi.org/10.1007/s13721-019-0207-3

    Article  Google Scholar 

  11. De Young GW, Keizer J (1992) A single-pool inositol 1,4,5-trisphosphate-receptor-based model for agonist-stimulated oscillations in Ca2+ concentration. Proc Natl Acad Sci USA 89(October):9895–9899. https://doi.org/10.1073/pnas.89.20.9895

    Article  PubMed  Google Scholar 

  12. Jha A, Adlakha N (2014) Analytical solution of two dimensional unsteady state problem of calcium diffusion in a neuron cell. J Med Imaging Health Inform 4(4):547–553. https://doi.org/10.1166/jmihi.2014.1282

    Article  Google Scholar 

  13. Jha A, Adlakha N (2015) Two-dimensional finite element model to study unsteady state Ca 2+ diffusion in neuron Involving ER, LEAK and SERCA. Int J Biomath 8(1):1–14. https://doi.org/10.1142/S1793524515500023

    Article  Google Scholar 

  14. Jha A, Adlakha N, Jha BK (2015) Finite element model to study effect of Na+-Ca2+ exchangers and source geometry on calcium Dynamics in a neuron cell. J Mech Med Biol 16(2):1–22. https://doi.org/10.1142/S0219519416500184

    Article  Google Scholar 

  15. Jha BK, Dave DD (2020) Approximation of calcium diffusion in Alzheimeric cell. J Multiscale Modell 11(2):1–21. https://doi.org/10.1142/S1756973720500018

    Article  Google Scholar 

  16. Jha BK, Jha A (2015) Two dimensional finite volume model to study the effect of ER on cytosolic calcium distribution in astrocytes. Proc Comput Sci 46:1285–1293. https://doi.org/10.1016/j.procs.2015.01.052

    Article  Google Scholar 

  17. Jha BK, Adlakha N, Mehta MN (2011) Finite Volume Model to Study the Effect of ER flux on Cytosolic Calcium Distribution in Astrocytes. J Comput 3(11):74–80, https://sites.google.com/site/Journal of Computing

  18. Jha BK, Adlakha N, Mehta M (2013) Two-dimensional finite element model to study calcium distribution in astrocytes in presence of VGCC and excess buffer. Int J Modeling Simul Sci Comput 4(2): 1250030-1-1250030-15 https://doi.org/10.1142/S1793962312500304

  19. Jha BK, Jha A, Adlakha N (2019) Three-dimensional finite element model to study calcium distribution in astrocytes in presence of VGCC and Excess. Differ Equ Dyn Syst. https://doi.org/10.1007/s12591-019-00502-x

    Article  Google Scholar 

  20. Kawamoto EM, Vivar C, Camandola S (2012) Physiology and pathology of calcium signaling in the brain. Front Pharmacol 3(April):1–17. https://doi.org/10.3389/fphar.2012.00061

    Article  CAS  Google Scholar 

  21. Keener J, Sneyd J (2009) Mathematical Physiology, 2nd edn. Springer, Berlin

    Book  Google Scholar 

  22. Khachaturian Z (1989) Introduction and Overview. Annals New York Academy of Sciences pp 4–7, https://doi.org/10.1111/j.1749-6632.1989.tb12485.x

  23. Khalid MU, Tervonen A, Korkka I, Hyttinen J, Lenk K (2018) Geometry-based Computational Modeling of Calcium Signaling in an Astrocyte. In: IFMBE Proceedings 65, Springer Nature Singapore Pvt Ltd., Tampere, Finland, pp 1–4, https://doi.org/10.1007/978-981-10-5122-7

  24. Laferla FM (2002) Calcium dyshomeostasis and intracellular signalling in Alzheimer’s Disease. Nat Rev Neurosci 3:862–872. https://doi.org/10.1038/nrn960

    Article  CAS  PubMed  Google Scholar 

  25. Magi S, Castaldo P, Macrì ML, Maiolino M, Matteucci A, Bastioli G, Gratteri S, Amoroso S, Lariccia V (2016) Intracellular calcium dysregulation : implications for Alzheimer ’ s Disease. Biomed Res Int 2016:1–14. https://doi.org/10.1155/2016/6701324

    Article  CAS  Google Scholar 

  26. Means S, Smith AJ, Shepherd J, Shadid J, Fowler J, Wojcikiewicz RJH, Mazel T, Smith GD, Wilson BS (2006) Reaction diffusion modeling of calcium dynamics with realistic ER geometry. Biophys J 91:537–557. https://doi.org/10.1529/biophysj.105.075036

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Naik P, Pardasani KR (2017) Three-dimensional finite element model to study calcium distribution in oocytes. Netw Modeling Anal Health Inform Bioinform. https://doi.org/10.1007/s13721-017-0158-5

    Article  Google Scholar 

  28. Naik PA, Pardasani KR (2015) Two-dimensional finite element model to study calcium distribution in oocytes. J Multiscale Model 6(1):1–15. https://doi.org/10.1142/S1756973714500024

    Article  CAS  Google Scholar 

  29. Naik PA, Pardasani KR (2016) Finite element model to study calcium distribution in oocytes involving voltage gated Ca 2 + channel, ryanodine receptor and buffers. Alexandria J Med 52(1):43–49. https://doi.org/10.1016/j.ajme.2015.02.002

    Article  Google Scholar 

  30. Naik PA, Pardasani KR (2018) Three-dimensional finite element model to study effect of RyR calcium channel, ER leak and SERCA pump on calcium distribution in oocyte cell. Int J Comput Methods 15(3):1–19. https://doi.org/10.1142/S0219876218500913

    Article  Google Scholar 

  31. Naik PA, Zu J (2020) Modeling and simulation of spatial-temporal calcium distribution in T lymphocyte cell by using a reaction-diffusion equation. J Bioinform Comput Biol Article. https://doi.org/10.1142/S0219720020500134

    Article  Google Scholar 

  32. Panday S, Pardasani KR (2013) Finite Element Model to Study Effect of Advection Diffusion and Na+/Ca2+ Exchanger on Ca2+ Distribution in oocytes. J Med Imaging Health Inform 3(3):374–379. https://doi.org/10.1166/jmihi.2013.1184

    Article  Google Scholar 

  33. Pathak K, Adlakha N (2015) Finite Element Model to Study Calcium Signalling in Cardiac Myocytes Involving Pump, Leak and Excess buffer. J Med Imaging Health Inform 5:1–6. https://doi.org/10.1166/jmihi.2015.1443

    Article  Google Scholar 

  34. Petersen OH (2017) The effects of Ca2+ buffers on cytosolic Ca2+ signalling. J Physiol 10:3107–3108. https://doi.org/10.1113/JP273852

    Article  CAS  Google Scholar 

  35. Popugaeva E, Bezprozvanny I, Stutzmann B, Franklin R (2013) Role of endoplasmic reticulum Ca 2+ signaling in the pathogenesis of Alzheimer disease. Front Mol Neurosci 6(September):1–7. https://doi.org/10.3389/fnmol.2013.00029

    Article  Google Scholar 

  36. Rajagopal S, Ponnusamy M (2017) Calcium signaling : from physiology to diseases. Springer Nature Singapore Pvt Ltd

  37. Riascos D, Leon DD, Baker-Nigh A, Nicholas A, Yukhananov R, Bu J, Wu CK, Geula C (2011) Age-related loss of calcium buffering and selective neuronal vulnerability in Alzheimer ’ s disease. Acta Neuropathol 122:565–576. https://doi.org/10.1007/s00401-011-0865-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Schampel A, Kuerten S (2017) Danger : high voltage–the role of voltage-gated system pathology. Cells 6:1–8. https://doi.org/10.3390/cells6040043

    Article  CAS  Google Scholar 

  39. Simms BA, Zamponi GW (2014) Neuronal voltage-gated calcium channels: structure, function, and dysfunction. NEURON 82(1):24–45. https://doi.org/10.1016/j.neuron.2014.03.016

    Article  CAS  PubMed  Google Scholar 

  40. Smith GD (1996) Analytical steady-state solution to the rapid buffering approximation bear an open Ca2+ channel. Biophys J 71:3064–3072. https://doi.org/10.1016/S0006-3495(96)79500-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Smith GD, Dai L, Miura RM, Sherman A (2001) Asymptotic analysis of buffered calcium diffusion near a point source. SIAM J Appl Math 61(5):1816–1838. https://doi.org/10.1137/S0036139900368996

    Article  CAS  Google Scholar 

  42. Supnet C, Bezprozvanny I (2010) Neuronal calcium signaling, mitochondrial dysfunction and Alzheimer’s disease. J Alzheimers Dis 20:S487–S498. https://doi.org/10.3233/JAD-2010-100306

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Tewari SG, Pardasani KR (2012) Modeling effect of sodium pump on calcium oscilations in neuron cells. J Multiscale Model 4(3):1–16. https://doi.org/10.1142/S1756973712500102

    Article  CAS  Google Scholar 

  44. Turkington C, Mitchell D (2010) The Encyclopedia of Alzheimer’s Disease, 2nd edn. An imprint of Infobase Publishing, Facts On File

  45. Wacquier B, Combettes L, Van Nhieu GT, Dupont G (2016) Interplay between intracellular ca 2+ oscillations and ca 2+-stimulated mitochondrial metabolism. Sci Rep 6(1):1–16. https://doi.org/10.1038/srep19316

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Devanshi D. Dave.

Ethics declarations

Conflicts of Interest

The authors declare that there is no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dave, D.D., Jha, B.K. Mathematical Modeling of Calcium Oscillatory Patterns in a Neuron. Interdiscip Sci Comput Life Sci 13, 12–24 (2021). https://doi.org/10.1007/s12539-020-00401-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12539-020-00401-8

Keywords

Navigation