Skip to main content
SpringerLink
Log in

Slow voltage inactivation of Ca2+ currents and bursting mechanisms for the mouse pancreatic beta-cell

  • Articles
  • Published:
The Journal of Membrane Biology Aims and scope Submit manuscript

Summary

Recent whole-cell electrophysiological data concerning the properties of the Ca2+ currents in mouse β -cells are fitted by a two-current model of Ca2+ channel kinetics. When the β -cell K+ currents are added to this model, only large modifications of the measured Ca2+ currents will reproduce the bursting pattern normally observed in mouse islets. However, when the measured Ca2+ currents are modified only slightly and used in conjunction with a K+ conductance that can be modulated dynamically by ATP concentration, reasonable bursting is obtained. Under these conditions it is the K-ATP conductance, rather than the slow voltage inactivation of the Ca2+ current, that determines the interburst interval. We find that this latter model can be reconciled with experiments that limit the possible periodic variation of the K-ATP conductance and with recent observations of intracellular Ca2+ bursting in islets

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

  • Ashcroft, F., Rorsman, P. 1989. Electrophysiology of the pancreatic β- cell. Prog. Biophys. Mol. Biol 54:87–143

    Google Scholar 

  • Ashcroft, S., Smith, P. 1989. Glucose modulates L-type Ca channels in murine isolated pancreatic β-cells. J. Physiol 417:79P

  • Atwater, I., Dawson, C., Scott, A., Eddleston, G., Rojas, E. 1980. Biochemistry and Biophysics of the Pancreatic β- cell. George Thieme, New York

    Google Scholar 

  • Chay, T. 1990. Effect of compartmentalized Ca ions on electrical bursting activity of pancreatic β-cells. Am. J. Physiol 258:C955-C965

    Google Scholar 

  • Chay, T., Keizer, J. 1983. Minimal model for membrane oscillations in the pancreatic β- cell. Biophys. J 42:181–190

    Google Scholar 

  • Cook, D., Ikeuchi, M. 1989. Tolbutamide as mimic of glucose on β- cell electrical activity, ATP-sensitive K− channels as common pathway for both stimuli. Diabetes 38:416–421

    Google Scholar 

  • Cook, D., Satin, L., Hopkins, W. 1991. Pancreatic β- cells are bursting, but how? Trends Neurosci 14:411–414

    Google Scholar 

  • Fatherazi, S., Cook, D.L. 1991. Specificity of tetraethylammonium and quinine for three K channels in insulin-secreting cells. J. Membrane Biol 120:105–114

    Google Scholar 

  • Henquin, J. 1990a. Glucose-induced electrical activity in β-cells, feedback control of ATP-sensitive K+ channels by Ca2+. Diabetes 39:1457–1460

    Google Scholar 

  • Henquin, J. 1990b. Role of voltage- and Ca2+-dependent K+ channels in the control of glucose-induced electrical activity in pancreatic β-cells. Pfluegers Arch 416:568–572

    Google Scholar 

  • Hopkins, W., Satin, L.S., Cook, D.L. 1991. Inactivation kinetics and pharmacology distinguish two calcium currents in mouse pancreatic β -cells. J. Membrane Biol 119:229–239

    Google Scholar 

  • Kakei, M., Kelly, R., Ashcroft, S., Ashcroft, S. 1986. The ATP-sensitivity of K+ channels in rat pancreatic β -cells is modulated by ADP. FEBS Lett 208:63–66

    Google Scholar 

  • Keizer, J., Magnus, G. 1989. ATP-sensitive potassium channels and bursting in the pancreatic β- cell. Biophys. J 56:229–242

    Google Scholar 

  • Keizer, J., Smolen, P. 1991. Bursting electrical activity in pancreatic beta cells caused by Ca2+-and voltage-inactivated Ca2+ channels. Proc. Natl. Acad. Sci. USA 88:3897–3901

    Google Scholar 

  • Kukuljan, M., Goncalves, A.A., Atwater, I. 1991. Charybdotoxin-sensitive KCa channel is not involved in glucose-induced electrical activity in pancreatic β -cells. J. Membrane Biol 119:187–195

    Google Scholar 

  • Lehninger, A. 1975. Biochemistry, pp. 531–533. Worth, New York

    Google Scholar 

  • Lenzen, S., Rustenbeck, I. 1991. Effects of IP3, spermine, and Mg2+ on regulation of Ca2+ transport by endoplasmic reticulum and mitochondria in permeabilized pancreatic islets. Diabetes 40:323–326

    Google Scholar 

  • Malecot, C., Feindt, P., Trautwein, W. 1988. Intracellular N-methyl-d-glucamine modifies the kinetics and voltage-dependence of the calcium current in guinea pig ventricular heart cells. Pfluegers Arch 411:235–242

    Google Scholar 

  • Misler, S., Falke, L., Gillis, K., McDaniel, M. 1986. A metabo-lite-regulated channel in rat pancreatic β -cells. Proc. Natl. Acad. Sci. USA 83:7119–7123

    Google Scholar 

  • Misler, S., Gee, W., Gillis, K., Scharp, D., Falke, L. 1989. Metabolite-regulated ATP-sensitive K+ channels in human pancreatic islet cells. Diabetes 38:422–427

    Google Scholar 

  • Plant, T. 1988. Properties and calcium-dependent inactivation of calcium currents in cultured mouse pancreatic β-cells, J. Physiol 404:731–747

    Google Scholar 

  • Rinzel, J. 1985. Bursting oscillations in an excitable membrane model. In: Ordinary and Partial Differential Equations. B. Sleeman and R. Jarvis, editors. pp. 304–316. Springer-Verlag, New York

    Google Scholar 

  • Rojas, E., Hidalgo, J., Carroll, P., Li, M., Atwater, I. 1990. A new class of calcium channels activated by glucose in human pancreatic β -cells. FEBS Lett 261:265–270

    Google Scholar 

  • Rorsman, P., Trube, G. 1986. Calcium and delayed potassium currents in mouse pancreatic β -cells under voltage-clamp conditions. J. Physiol 374:531–550

    Google Scholar 

  • Santos, R., Rosario, L., Nadal, A., Garcia-Sancho, J., Soria, B., Valdeolmillos, M. 1991. Widespread synchronous Ca2+ oscillations due to bursting electrical activity in single pancreatic islets. Pfluegers Arch 418:417–422

    Google Scholar 

  • Satin, L., Cook, D. 1988. Evidence for two calcium currents in insulin-secreting cells. Pfluegers Arch 411:401–409

    Google Scholar 

  • Satin, L., Cook, D. 1989. Calcium current inactivation in insulin-secreting cells is mediated by calcium influx and membrane depolarization. Pfluegers Arch 414:1–10

    Google Scholar 

  • Sherman, A., Keizer, J., Rinzel, J. 1990. Domain model for Ca2−-inactivation of Ca2+ channels at low channel density. Biophys. J 58:985–995

    Google Scholar 

  • Sherman, A., Rinzel, J., Keizer, J. 1988. Emergence of organized bursting in clusters of pancreatic β -cells by channel sharing. Biophys. J 54:411–425

    Google Scholar 

  • Smith, P., Ashcroft, F., Rorsman, P. 1990. Simultaneous recordings of glucose dependent electrical activity and ATP-regulated K+-currents in isolated mouse pancreatic β -cells. FEBS Lett 261:187–190

    Google Scholar 

  • Valdeolmillos, M., Santos, R., Contreras, D., Soria, B., Rosario, L. 1989. Glucose-induced oscillations of intracellular Ca2+ concentration resembling bursting electrical activity in single mouse islets of Langerhans. FEBS Lett 259:19–23

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Mathematical Research Branch, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, 20892, Bethesda, Maryland

    Paul Smolen

  2. Institute of Theoretical Dynamics and Department of Chemistry, University of California, 95616, Davis, California

    Joel Keizer

Authors
  1. Paul Smolen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Joel Keizer
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

This work was supported in part by NSF grant DIR-90-06104 and the Agricultural Experiment Station of the University of California. P.S. gratefully acknowledges financial support from an NRC Fellowship. We have benefited from numerous conversations with Drs. John Rinzel, Arthur Sherman, Daniel Cook, and Leslie Satin

Rights and permissions

Reprints and permissions

About this article

Cite this article

Smolen, P., Keizer, J. Slow voltage inactivation of Ca2+ currents and bursting mechanisms for the mouse pancreatic beta-cell. J. Membarin Biol 127, 9–19 (1992). https://doi.org/10.1007/BF00232754

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00232754

Key words

Search

Navigation