Skip to main content
NCBI home page
Biochemical Journal logoLink to Biochemical Journal
. 1996 Feb 15;314(Pt 1):167–173. doi: 10.1042/bj3140167

Comparison of the effects of perchlorate and Bay K 8644 on the dynamics of cytoplasmic Ca2+ concentration and insulin secretion in mouse beta-cells.

G Larsson-Nyrén 1, J Sehlin 1
PMCID: PMC1217021  PMID: 8660279

Abstract

Non-inbred ob/ob mice were used to study the dynamics of cytoplasmic Ca2+ concentration ([Ca2+]i) in isolated pancreatic beta-cells using microfluorimetry with fura 2/AM as probe, and the dynamics of insulin secretion in isolated pancreatic islets. D-Glucose (20 mM) caused a transient peak increase in [CA2+]i which changed to either an oscillating or a flat, elevated phase. The lag-time before the first peak increase in [Ca2+]i was markedly shortened by 12 mM ClO4- and the glucose-stimulated level of [Ca2+]i after the first peak was clearly elevated by the anion. ClO4- did not change the basal [Ca2+]i at 3 mM glucose. Extracellular Ca2+ deficiency abolished the effect of high glucose and ClO4- on [Ca2+]i. This suggests that ClO4- acts as an amplifier of transmembrane Ca2+ inflow. The L-type Ca2+ channel agonist, Bay K 8644 (0.01-1.0 microM), strictly reproduced all the effects of perchlorate on the glucose-stimulated beta-cell [Ca2+]i. Both phases of insulin release (20 mM glucose) were markedly enhanced by ClO4- (12 mM) or Bay K 8644 (1.0 microM). The lag-time for glucose-stimulated insulin release was shortened by both agents. Taken together, these data strengthen the idea that perchlorate amplifies the glucose-stimulation of [Ca2+]i and insulin release by directly modifying the function of the L-type Ca2+ channel. This effect can induce both a more prompt onset of and an amplified level of beta-cell secretory activity.

Full Text

The Full Text of this article is available as a PDF (592.5 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ashcroft F. M., Rorsman P. Electrophysiology of the pancreatic beta-cell. Prog Biophys Mol Biol. 1989;54(2):87–143. doi: 10.1016/0079-6107(89)90013-8. [DOI] [PubMed] [Google Scholar]
  2. Bechem M., Hoffmann H. The molecular mode of action of the Ca agonist (-) BAY K 8644 on the cardiac Ca channel. Pflugers Arch. 1993 Aug;424(3-4):343–353. doi: 10.1007/BF00384362. [DOI] [PubMed] [Google Scholar]
  3. Catterall W. A., Striessnig J. Receptor sites for Ca2+ channel antagonists. Trends Pharmacol Sci. 1992 Jun;13(6):256–262. doi: 10.1016/0165-6147(92)90079-l. [DOI] [PubMed] [Google Scholar]
  4. Csernoch L., Kovács L., Szücs G. Perchlorate and the relationship between charge movement and contractile activation in frog skeletal muscle fibres. J Physiol. 1987 Sep;390:213–227. doi: 10.1113/jphysiol.1987.sp016695. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Gallant E. M., Taus N. S., Fletcher T. F., Lentz L. R., Louis C. F., Mickelson J. R. Perchlorate potentiation of excitation-contraction coupling in mammalian skeletal muscles. Am J Physiol. 1993 Mar;264(3 Pt 1):C559–C567. doi: 10.1152/ajpcell.1993.264.3.C559. [DOI] [PubMed] [Google Scholar]
  6. Gomolla M., Gottschalk G., Lüttgau H. C. Perchlorate-induced alterations in electrical and mechanical parameters of frog skeletal muscle fibres. J Physiol. 1983 Oct;343:197–214. doi: 10.1113/jphysiol.1983.sp014888. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Grapengiesser E., Gylfe E., Hellman B. Three types of cytoplasmic Ca2+ oscillations in stimulated pancreatic beta-cells. Arch Biochem Biophys. 1989 Jan;268(1):404–407. doi: 10.1016/0003-9861(89)90602-4. [DOI] [PubMed] [Google Scholar]
  8. Grynkiewicz G., Poenie M., Tsien R. Y. A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem. 1985 Mar 25;260(6):3440–3450. [PubMed] [Google Scholar]
  9. Hahn H. J., Hellman B., Lernmark A., Sehlin J., Täljedal I. B. The pancreatic beta-cell recognition of insulin secretogogues. Influence of neuraminidase treatment on the release of insulin and the islet content of insulin, sialic acid, and cyclic adenosine 3':5'-monophosphate. J Biol Chem. 1974 Aug 25;249(16):5275–5284. [PubMed] [Google Scholar]
  10. Hellman B., Idahl L. A., Lernmark A., Sehlin J., Täljedal I. B. The pancreatic beta-cell recognition of insulin secretagogues. Effects of calcium and sodium on glucose metabolism and insulin release. Biochem J. 1974 Jan;138(1):33–45. doi: 10.1042/bj1380033. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hellman B. Studies in obese-hyperglycemic mice. Ann N Y Acad Sci. 1965 Oct 8;131(1):541–558. doi: 10.1111/j.1749-6632.1965.tb34819.x. [DOI] [PubMed] [Google Scholar]
  12. Hess P., Lansman J. B., Tsien R. W. Different modes of Ca channel gating behaviour favoured by dihydropyridine Ca agonists and antagonists. Nature. 1984 Oct 11;311(5986):538–544. doi: 10.1038/311538a0. [DOI] [PubMed] [Google Scholar]
  13. Huang C. L. 'Off' tails of intramembrane charge movements in frog skeletal muscle in perchlorate-containing solutions. J Physiol. 1987 Mar;384:491–509. doi: 10.1113/jphysiol.1987.sp016466. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Idahl L. A. Dynamics of pancreatic beta-cell responses to glucose. Diabetologia. 1973 Oct;9(5):403–412. doi: 10.1007/BF01239437. [DOI] [PubMed] [Google Scholar]
  15. Kokubun S., Reuter H. Dihydropyridine derivatives prolong the open state of Ca channels in cultured cardiac cells. Proc Natl Acad Sci U S A. 1984 Aug;81(15):4824–4827. doi: 10.1073/pnas.81.15.4824. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Larsson-Nyrén G., Sehlin J. Interaction between perchlorate and nifedipine on insulin secretion from mouse pancreatic islets. Biosci Rep. 1993 Apr;13(2):107–117. doi: 10.1007/BF01145963. [DOI] [PubMed] [Google Scholar]
  17. Lebrun P., Atwater I. Effects of the calcium channel agonist, BAY K 8644, on electrical activity in mouse pancreatic B-cells. Biophys J. 1985 Dec;48(6):919–930. doi: 10.1016/S0006-3495(85)83855-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lernmark A. The preparation of, and studies on, free cell suspensions from mouse pancreatic islets. Diabetologia. 1974 Oct;10(5):431–438. doi: 10.1007/BF01221634. [DOI] [PubMed] [Google Scholar]
  19. Lindström P., Sehlin J. 5-hydroxytryptamine stimulates 86Rb+ efflux from pancreatic beta-cells. Biochim Biophys Acta. 1982 Jul 22;720(4):400–404. doi: 10.1016/0167-4889(82)90118-5. [DOI] [PubMed] [Google Scholar]
  20. Lindström P., Sehlin J. Mechanisms underlying the effects of 5-hydroxytryptamine and 5-hydroxytryptophan in pancreatic islets. A proposed role for L-aromatic amino acid decarboxylase. Endocrinology. 1983 Apr;112(4):1524–1529. doi: 10.1210/endo-112-4-1524. [DOI] [PubMed] [Google Scholar]
  21. Lüttgau H. C., Gottschalk G., Kovács L., Fuxreiter M. How perchlorate improves excitation-contraction coupling in skeletal muscle fibers. Biophys J. 1983 Aug;43(2):247–249. doi: 10.1016/S0006-3495(83)84346-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Ma J., Anderson K., Shirokov R., Levis R., González A., Karhanek M., Hosey M. M., Meissner G., Ríos E. Effects of perchlorate on the molecules of excitation-contraction coupling of skeletal and cardiac muscle. J Gen Physiol. 1993 Sep;102(3):423–448. doi: 10.1085/jgp.102.3.423. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Malaisse-Lagae F., Mathias P. C., Malaisse W. J. Gating and blocking of calcium channels by dihydropyridines in the pancreatic B-cell. Biochem Biophys Res Commun. 1984 Sep 28;123(3):1062–1068. doi: 10.1016/s0006-291x(84)80241-7. [DOI] [PubMed] [Google Scholar]
  24. McLaughlin S., Bruder A., Chen S., Moser C. Chaotropic anions and the surface potential of bilayer membranes. Biochim Biophys Acta. 1975 Jun 25;394(2):304–313. doi: 10.1016/0005-2736(75)90267-9. [DOI] [PubMed] [Google Scholar]
  25. Nowycky M. C., Fox A. P., Tsien R. W. Three types of neuronal calcium channel with different calcium agonist sensitivity. Nature. 1985 Aug 1;316(6027):440–443. doi: 10.1038/316440a0. [DOI] [PubMed] [Google Scholar]
  26. Ohlsson L., Lindström P., Sehlin J. Perchlorate stimulates potassium-induced growth hormone release in cultured rat somatotrophs. Acta Physiol Scand. 1989 Dec;137(4):545–546. doi: 10.1111/j.1748-1716.1989.tb08793.x. [DOI] [PubMed] [Google Scholar]
  27. Ríos E., Karhanek M., Ma J., González A. An allosteric model of the molecular interactions of excitation-contraction coupling in skeletal muscle. J Gen Physiol. 1993 Sep;102(3):449–481. doi: 10.1085/jgp.102.3.449. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Sandström P. E., Sehlin J. Furosemide-induced glucose intolerance in mice is associated with reduced insulin secretion. Eur J Pharmacol. 1988 Mar 15;147(3):403–409. doi: 10.1016/0014-2999(88)90175-6. [DOI] [PubMed] [Google Scholar]
  29. Schramm M., Thomas G., Towart R., Franckowiak G. Novel dihydropyridines with positive inotropic action through activation of Ca2+ channels. Nature. 1983 Jun 9;303(5917):535–537. doi: 10.1038/303535a0. [DOI] [PubMed] [Google Scholar]
  30. Sehlin J. Effect of perchlorate on calcium uptake and insulin secretion in mouse pancreatic islets. Biochem J. 1987 Nov 15;248(1):109–115. doi: 10.1042/bj2480109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Smith P. A., Rorsman P., Ashcroft F. M. Modulation of dihydropyridine-sensitive Ca2+ channels by glucose metabolism in mouse pancreatic beta-cells. Nature. 1989 Nov 30;342(6249):550–553. doi: 10.1038/342550a0. [DOI] [PubMed] [Google Scholar]
  32. Stauffacher W., Lambert A. E., Vecchio D., Renold A. E. Measurements of insulin activities in pancreas and serum of mice with spontaneous ("Obese" and "New Zealand Obese") and induced (Goldthioglucose) obesity and hyperglycemia, with considerations on the pathogenesis of the spontaneous syndrome. Diabetologia. 1967 Apr;3(2):230–237. doi: 10.1007/BF01222200. [DOI] [PubMed] [Google Scholar]
  33. Stauffacher W., Renold A. E. Effect of insulin in vivo on diaphragm and adipose tissue of obese mice. Am J Physiol. 1969 Jan;216(1):98–105. doi: 10.1152/ajplegacy.1969.216.1.98. [DOI] [PubMed] [Google Scholar]
  34. Von Hippel P. H., Peticolas V., Schack L., Karlson L. Model studies on the effects of neutral salts on the conformational stability of biological macromolecules. I. Ion binding to polyacrylamide and polystyrene columns. Biochemistry. 1973 Mar 27;12(7):1256–1264. doi: 10.1021/bi00731a003. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES