Skip to main content
SpringerLink
Log in

The Role of G-Proteins in the Regulation of Pacemaking Activity

  • Published:
Annals of Biomedical Engineering Aims and scope Submit manuscript

Abstract

This work is concerned with modeling the key interrelated biochemical reactions involved in initiating and inhibiting pacemaking activity in the mammalian sinoatrial node. A detailed model involving G-proteins was developed to better represent the activation pathway for adenylate cyclase. Concentration profiles of an activated G-protein complex [αTC] were established as a function of the membrane bound calcium calmodulin concentration. A previously developed model used to establish temporal profiles of cAMP was improved using the G-protein effects through the [αTC] functionality. Methods were also developed to model inhibition of G-protein by acetylcholine. Analytical solutions were developed to predict acetylcholine concentration profiles as a function of diffusion parameter and duration of acetylcholine pulses. The model was used to demonstrate suppression of cAMP by acetylcholine through G-protein pathways. It provides a basis for a tool to quantify key biochemical species during stimulation and inhibition of sinoatrial node pacemaking. A stability analysis of the model equations has potential application in studying the link between the biochemical species concentrations and abnormal effects in sinoatrial node pacemaking. © 1999 Biomedical Engineering Society.

PAC99: 8710+e, 8714Ee, 8719Nn, 8719Hh, 8717Aa

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  1. Brown, H. F., D. Noble, S. I. Noble, and A. I. Taupigan, Physiol. (Paris) 29:370, 1986.

    Google Scholar 

  2. Brown, A. M., A. Yatani, Y. Imoto, J. Codina, R. Mattera, and L. Birnbaumer, Ann. (N.Y.) Acad. Sci. 560:373, 1989.

    Google Scholar 

  3. Demir, S. S., J. W. Clark, C. R. Murphey, and W. R. Giles, Am. J. Physiol. 266:C832-C852, 1994.

    Google Scholar 

  4. Demir, S. S., J. W. Clark, C. R. Murphey, and W. R. Giles, Am. J. Physiol. 276:H2221-H2244, 1999.

    Google Scholar 

  5. DiFrancesco, D. and D. Noble, Philos. Trans. R. Soc. London 307:353, 1985.

    Google Scholar 

  6. DiFrancesco, D., and C. Tromba, Pflugers Arch. Ges. Physiol. Menschen Tiere 410:139–142, 1987.

    Google Scholar 

  7. Dokos, S., B. G. Celler, and N. H. Lovell, Biomed. Eng. 21:321–335, 1993.

    Google Scholar 

  8. Dokos, S., B. Celler, and N. Lovell, J. Theor. Biol. 181:245–272, 1996.

    Google Scholar 

  9. Dokos, S., B. G. Celler, and N. H. Lovell, J. Theor. Biol. 182:21–44, 1996.

    Google Scholar 

  10. Dokos, S., B. G. Celler, and N. H. Lovell, Biomed. Eng. 25:769–782, 1997.

    Google Scholar 

  11. Gilman, A. G., Cell 36:577–579, 1984.

    Google Scholar 

  12. Gilman, A. G., Annu. Rev. Biochem. 56:615, 1987.

    Google Scholar 

  13. Goldberger, A. L., and E. Goldberger, Clinical Electrocardiography—A Simplified Approach, 3rd ed., New Delhi: Jaycee Brothers, 1986, p. 3.

    Google Scholar 

  14. Hagiwara, N., H. Irisawa, and M. Kameyama, J. Physiol. (Paris) 395:233–253, 1988.

    Google Scholar 

  15. Hischeler, J., M. Kameyama, and W. Trautwein, Pflugers Arch. Ges. Physiol. Menschen Tiere 407:182–189, 1986.

    Google Scholar 

  16. Irisawa, H., H. F. Brown, and W. Giles, Cardiac Pacemaking in Sinoatrial Node. Physiol. Rev. 73:1, 1993.

    Google Scholar 

  17. Iyengar, R., and Birnbaumer, L. G., ed., G. Proteins, New York: Academic 1990, p. 1.

    Google Scholar 

  18. Kale, S. S. Mathematical modeling of the biochemical reactions of initiation and inhibition of sinoatrial node pacemaking, PhD dissertation, Department of Chemical and Biochemical Engineering, Rutgers University, 1996.

  19. Nho, K. Dual functionality of calmodulin in cell activation, PhD dissertation, Department of Chemical and Biochemical Engineering, Rutgers University, 1989.

  20. Petzold, L. R. Sandia Report No. Sand 82–863, 1982.

  21. Premont, R. T., and R. Iyengar, in Ref. 17, p. 147.

  22. Rasmusson, R. L., J. W. Clark, W. R. Giles, E. F. Shibata, and D. L. Campbell, J. Am. Physiol. Soc. 363:6135, 1990.

    Google Scholar 

  23. Rodbell, M., L. Birnhauser, S. L. Pohl, and H. M. J. Krans, J. Biol. Chem. 246:1877, 1971.

    Google Scholar 

  24. Vieth, W. R., Membrane Systems: Analysis and Design, New York: Wiley, 1994, p. 318.

    Google Scholar 

  25. Vieth, W. R., K. Nho, and S. S. Kale, Adv. Biomed. Eng. 21:669, 1993.

    Google Scholar 

  26. Wang, Y., and S. L. Lipsius, Circ. Res. 79:109–114, 1996.

    Google Scholar 

  27. Wilders, R., H. J. Jongsma, and C. G. Van Ginneken, Biophys. J. 60:1202–1216, 1991.

    Google Scholar 

  28. Yatani, A., J. Codina, and A. M. Brown, in Ref. 17, p. 241.

Download references

Author information

Authors and Affiliations

  1. Consulting Chemical Engineer, Houston, TX

    S. S. Kale

  2. Department of Chemical and Biochemical Engineering, Rutgers University, USA

    W. R. Vieth

Authors
  1. S. S. Kale
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. W. R. Vieth
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. K. Nho
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kale, S.S., Vieth, W.R. & Nho, K. The Role of G-Proteins in the Regulation of Pacemaking Activity. Annals of Biomedical Engineering 27, 746–757 (1999). https://doi.org/10.1114/1.228

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1114/1.228

Search

Navigation