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. 1999 Jul;77(1):45–53. doi: 10.1016/S0006-3495(99)76871-2

Effect of Na/Ca exchange on plateau fraction and [Ca]i in models for bursting in pancreatic beta-cells.

D Gall 1, I Susa 1
PMCID: PMC1300311  PMID: 10388739

Abstract

In the presence of an insulinotropic glucose concentration, beta-cells, in intact pancreatic islets, exhibit periodic bursting electrical activity consisting of an alternation of active and silent phases. The fraction of time spent in the active phase over a period is called the plateau fraction and is correlated with the rate of insulin release. However, the mechanisms that regulate the plateau fraction remain unclear. In this paper we investigate the possible role of the plasma membrane Na+/Ca2+ exchange of the beta-cell in controlling the plateau fraction. We have extended different single-cell models to incorporate this Ca2+-activated electrogenic Ca2+ transporter. We find that the Na+/Ca2+ exchange can provide a physiological mechanism to increase the plateau fraction as the glucose concentration is raised. In addition, we show theoretically that the Na+/Ca2+ exchanger is a key regulator of the cytoplasmic calcium concentration in clusters of heterogeneous cells with gap-junctional electrical coupling.

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Selected References

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  1. Atwater I., Dawson C. M., Scott A., Eddlestone G., Rojas E. The nature of the oscillatory behaviour in electrical activity from pancreatic beta-cell. Horm Metab Res Suppl. 1980;Suppl 10:100–107. [PubMed] [Google Scholar]
  2. Bers D. M. Species differences and the role of sodium-calcium exchange in cardiac muscle relaxation. Ann N Y Acad Sci. 1991;639:375–385. doi: 10.1111/j.1749-6632.1991.tb17326.x. [DOI] [PubMed] [Google Scholar]
  3. Blaustein M. P., Hodgkin A. L. The effect of cyanide on the efflux of calcium from squid axons. J Physiol. 1969 Feb;200(2):497–527. doi: 10.1113/jphysiol.1969.sp008704. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bokvist K., Eliasson L., Ammälä C., Renström E., Rorsman P. Co-localization of L-type Ca2+ channels and insulin-containing secretory granules and its significance for the initiation of exocytosis in mouse pancreatic B-cells. EMBO J. 1995 Jan 3;14(1):50–57. doi: 10.1002/j.1460-2075.1995.tb06974.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chay T. R. Effects of extracellular calcium on electrical bursting and intracellular and luminal calcium oscillations in insulin secreting pancreatic beta-cells. Biophys J. 1997 Sep;73(3):1673–1688. doi: 10.1016/S0006-3495(97)78199-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dean P. M., Matthews E. K. Glucose-induced electrical activity in pancreatic islet cells. J Physiol. 1970 Sep;210(2):255–264. doi: 10.1113/jphysiol.1970.sp009207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Egan T. M., Noble D., Noble S. J., Powell T., Spindler A. J., Twist V. W. Sodium-calcium exchange during the action potential in guinea-pig ventricular cells. J Physiol. 1989 Apr;411:639–661. doi: 10.1113/jphysiol.1989.sp017596. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Ehara T., Matsuoka S., Noma A. Measurement of reversal potential of Na+-Ca2+ exchange current in single guinea-pig ventricular cells. J Physiol. 1989 Mar;410:227–249. doi: 10.1113/jphysiol.1989.sp017530. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. HODGKIN A. L., HUXLEY A. F. A quantitative description of membrane current and its application to conduction and excitation in nerve. J Physiol. 1952 Aug;117(4):500–544. doi: 10.1113/jphysiol.1952.sp004764. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hellman B., Andersson T., Berggren P. O., Rorsman P. Calcium and pancreatic beta-cell function. XI. Modification of 45Ca fluxes by Na+ removal. Biochem Med. 1980 Oct;24(2):143–152. doi: 10.1016/0006-2944(80)90005-8. [DOI] [PubMed] [Google Scholar]
  11. Herchuelz A., Sener A., Malaisse W. J. Regulation of calcium fluxes in rat pancreatic islets: calcium extrusion by sodium-calcium countertransport. J Membr Biol. 1980 Nov 15;57(1):1–12. doi: 10.1007/BF01868981. [DOI] [PubMed] [Google Scholar]
  12. Hilgemann D. W., Collins A., Matsuoka S. Steady-state and dynamic properties of cardiac sodium-calcium exchange. Secondary modulation by cytoplasmic calcium and ATP. J Gen Physiol. 1992 Dec;100(6):933–961. doi: 10.1085/jgp.100.6.933. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hilgemann D. W. The cardiac Na-Ca exchanger in giant membrane patches. Ann N Y Acad Sci. 1996 Apr 15;779:136–158. doi: 10.1111/j.1749-6632.1996.tb44783.x. [DOI] [PubMed] [Google Scholar]
  14. Kimura J., Noma A., Irisawa H. Na-Ca exchange current in mammalian heart cells. Nature. 1986 Feb 13;319(6054):596–597. doi: 10.1038/319596a0. [DOI] [PubMed] [Google Scholar]
  15. Kukuljan M., Goncalves A. A., Atwater I. Charybdotoxin-sensitive K(Ca) channel is not involved in glucose-induced electrical activity in pancreatic beta-cells. J Membr Biol. 1991 Jan;119(2):187–195. doi: 10.1007/BF01871418. [DOI] [PubMed] [Google Scholar]
  16. Meissner H. P. Electrophysiological evidence for coupling between beta cells of pancreatic islets. Nature. 1976 Aug 5;262(5568):502–504. doi: 10.1038/262502a0. [DOI] [PubMed] [Google Scholar]
  17. Meissner H. P., Schmelz H. Membrane potential of beta-cells in pancreatic islets. Pflugers Arch. 1974;351(3):195–206. doi: 10.1007/BF00586918. [DOI] [PubMed] [Google Scholar]
  18. Miura Y., Kimura J. Sodium-calcium exchange current. Dependence on internal Ca and Na and competitive binding of external Na and Ca. J Gen Physiol. 1989 Jun;93(6):1129–1145. doi: 10.1085/jgp.93.6.1129. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Noble D., Noble S. J., Bett G. C., Earm Y. E., Ho W. K., So I. K. The role of sodium-calcium exchange during the cardiac action potential. Ann N Y Acad Sci. 1991;639:334–353. doi: 10.1111/j.1749-6632.1991.tb17323.x. [DOI] [PubMed] [Google Scholar]
  20. Perez-Armendariz E., Atwater I., Rojas E. Glucose-induced oscillatory changes in extracellular ionized potassium concentration in mouse islets of Langerhans. Biophys J. 1985 Nov;48(5):741–749. doi: 10.1016/S0006-3495(85)83832-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Reuter H., Seitz N. The dependence of calcium efflux from cardiac muscle on temperature and external ion composition. J Physiol. 1968 Mar;195(2):451–470. doi: 10.1113/jphysiol.1968.sp008467. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Saha S., Grapengiesser E. Glucose promotes turnover of Na+ in pancreatic beta-cells. Biochim Biophys Acta. 1995 Mar 16;1265(2-3):209–212. doi: 10.1016/0167-4889(94)00234-6. [DOI] [PubMed] [Google Scholar]
  23. Santos R. M., Rosario L. M., Nadal A., Garcia-Sancho J., Soria B., Valdeolmillos M. Widespread synchronous [Ca2+]i oscillations due to bursting electrical activity in single pancreatic islets. Pflugers Arch. 1991 May;418(4):417–422. doi: 10.1007/BF00550880. [DOI] [PubMed] [Google Scholar]
  24. Sherman A. Contributions of modeling to understanding stimulus-secretion coupling in pancreatic beta-cells. Am J Physiol. 1996 Aug;271(2 Pt 1):E362–E372. doi: 10.1152/ajpendo.1996.271.2.E362. [DOI] [PubMed] [Google Scholar]
  25. Sherman A., Rinzel J., Keizer J. Emergence of organized bursting in clusters of pancreatic beta-cells by channel sharing. Biophys J. 1988 Sep;54(3):411–425. doi: 10.1016/S0006-3495(88)82975-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Smolen P., Rinzel J., Sherman A. Why pancreatic islets burst but single beta cells do not. The heterogeneity hypothesis. Biophys J. 1993 Jun;64(6):1668–1680. doi: 10.1016/S0006-3495(93)81539-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Van Eylen F., Svoboda M., Herchuelz A. Identification, expression pattern and potential activity of Na/Ca exchanger isoforms in rat pancreatic B-cells. Cell Calcium. 1997 Mar;21(3):185–193. doi: 10.1016/s0143-4160(97)90043-9. [DOI] [PubMed] [Google Scholar]
  28. Wesslén N., Bergsten P., Hellman B. Glucose-induced reduction of the sodium content in beta-cell-rich pancreatic islets. Biosci Rep. 1986 Nov;6(11):967–972. doi: 10.1007/BF01114973. [DOI] [PubMed] [Google Scholar]

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