Skip to main content
Log in

Concentration-dependent modulations of potassium and calcium currents of rat osteoblastic cells by arachidonic acid

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

Abstract

We show that the voltage-gated K+ and Ca2+ currents of rat osteoblastic cells are strongly modulated by arachidonic acid (AA), and that these modulations are very sensitive to the AA concentration. At 2 or 3 μm, AA reduces the amplitude and accelerates the inactivation of the K+ current activated by depolarization; at higher concentrations (≥5 μm), AA still blocks this K+ current, but also induces a very large noninactivating K+ current. At 2 or 3 μm, AA enhances the T-type Ca2+ current, close to its threshold of activation, whereas at 10 μm, it blocks that current. AA (1–10 μm) also blocks the dihydropyridine-sensitive L-type Ca2+ current. Thus, the effect of AA on Ca2+ entry through voltage-gated Ca2+ channels can change qualitatively with the AA concentration: at 2 or 3 μm, AA will favor Ca2+ entry through T channels, both by lowering the voltage-gated K+ conductance and by increasing the T current, whereas at 10 μm, AA will prevent Ca2+ entry through voltage-gated Ca2+ channels, both by inducing a K+ conductance and by blocking Ca2+ channels.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Amagai, Y., Kasai, S. 1989. A voltage-dependent calcium current in mouse MC3T3-E1 osteogenic cells. Jap. J. Physiol. 39:773–777

    Google Scholar 

  2. Béhé, P., Sandmeier, K., Meves, H. 1992. The effect of arachidonic acid on the M current of NG 108–15 neuroblastoma x glioma hybrid cells. Pfluegers Arch. 422:120–128

    Google Scholar 

  3. Binderman, I., Zor, U., Kaye, A.M., Shimshoni, Z., Harell, A., Sömjen, D. 1988. The transduction of mechanical force into biochemical events in bone cells may involve activation of phospholipase A2. Calcif. Tissue Int. 42:261–266

    Google Scholar 

  4. Braughler, J.M., Mittal, C.K., Murad, F. 1979. Purification of soluble guanylate cyclase from rat liver. Proc. Natl. Acad. Sci. USA 76:219–222

    Google Scholar 

  5. Caffrey, J.M., Farach-Carson, M.C. 1989. Vitamin D3 metabolites modulate dihydropyridine-sensitive calcium currents in clonal rat osteosarcoma cells. J. Biol. Chem. 264:20265–20274

    Google Scholar 

  6. Chesnoy-Marchais, D., Fritsch, J. 1988. Voltage-gated sodium and calcium currents in rat osteoblasts. J. Physiol. 398:291–311

    Google Scholar 

  7. Chesnoy-Marchais, D., Fritsch, J. 1993. Potassium currents and effects of vitamin D3 metabolites and cyclic GMP in rat osteoblastic cells. Biochim. Biophys. Acta 1148:239–248

    Google Scholar 

  8. Davidson, R.M., Tatakis, D.W., Auerbach, A.L. 1990. Multiple forms of mechanosensitive ion channels in osteoblast-like cells. Pfluegers Arch. 416:646–651

    Google Scholar 

  9. Duncan, R., Misler S., 1989. Voltage-activated and stretch-activated Ba2+ conducting channels in an osteoblast-like cell line (UMR 106). FEBS Lett. 251:17–21

    Google Scholar 

  10. Ellies, L.G., Heersche, J.N.M., Vadas, P., Pruzanski, W., Stefanski, E., Aubin, J.E. 1991. Interleukin-1 α stimulates the release of prostaglandin E2 and phospholipase A2 from fetal rat calvarial cells in vitro: relationship to bone nodule formation. J. Bone Min. Res. 6:843–850

    Google Scholar 

  11. Ferrier, J., Ward-Kesthely, A., Homble, F., Ross, S. 1987. Further analysis of spontaneous membrane potential activity and the hyperpolarizing response to parathyroid hormone in osteoblastlike cells. J. Cell. Physiol. 130:344–351

    Google Scholar 

  12. Fujimori, A., Tsutsumi, M., Yamada, H., Fukase, M., Fujita, T. 1989. Arachidonic acid stimulates cell growth in an osteoblastic cell line, MC3T3-E1, by noneicosanoid mechanism. Calcif. Tissue Int. 44:186–191

    Google Scholar 

  13. Grygorczyk, C., Grygorczyk, R., Ferrier, J. 1989. Osteoblastic cells have L-type calcium channels. Bone and Mineral 7:137–148

    Google Scholar 

  14. Guggino, S.E., Lajeunesse, D., Wagner, J.A., Snyder, S.H. 1989. Bone remodeling signaled by a dihydropyridineand phenylalkylamine-sensitive calcium channel. Proc. Natl. Acad. Sci. USA 86:2957–2960

    Google Scholar 

  15. Keyser, D.O., Alger, B.E. 1990. Arachidonic acid modulates hippocampal calcium current via protein kinase C and oxygen radicals. Neuron 5:545–553

    Google Scholar 

  16. Kim, D., Clapham, D.E. 1989. Potassium channels in cardiac cells activated by arachidonic acid and phospholipids. Science 244:1174–1176

    Google Scholar 

  17. Kim, D., Lewis, D.L., Graziadei, L., Neer, E.J., Bar-Sagi, D., Clapham, D.E. 1989. G-protein βγ-subunits activate the cardiac muscarinic K+-channel via phospholipase A2. Nature 337:557–560

    Google Scholar 

  18. Kirber, M.T., Ordway, R.W., Clapp, L.H., Walsh, J.V., Singer, J.J. 1992. Both membrane stretch and fatty acids directly activate large conductance Ca2+-activated K+ channels in vascular smooth muscle cells. FEBS Lett. 297:24–28

    Google Scholar 

  19. Kozawa, O., Tokuda, H., Miwa, M., Takahashi, Y., Ozaki, N., Oiso, Y. 1992. Mechanism of prostaglandin E2-induced arachidonic acid release in osteoblast-like cells: independence from phosphoinositide hydrolysis. Prostaglandins Leukotrienes and Essential Fatty Acids 46:291–295

    Google Scholar 

  20. Kurachi, Y., Ito, H., Sugimoto, T., Shimizu, T., Miki, I., Ui, M. 1989. Arachidonic acid metabolites as intracellular modulators of the G protein-gated cardiac K+ channel. Nature 337:555–557

    Google Scholar 

  21. Linden, D.J., Routtenberg, A. 1989. Cis-fatty acids, which activate protein kinase C, attenuate Na+ and Ca2+ currents in mouse neuroblastoma cells. J. Physiol. 419:95–119

    Google Scholar 

  22. Ljunggren, O., Vavrek, R., Stewart, J.M., Lerner, U.H. 1991. Bradykinin-induced burst of prostaglandin formation in osteoblasts is mediated via B2 bradykinin receptors. J. Bone Miner. Res. 6:807–815

    Google Scholar 

  23. Morain, P., Peglion, J.L., Giesen-Grouse, E. 1992. Ca2+ channel inhibition in a rat osteoblast-like cell line, UMR 106, by a new dihydropyridine derivative, S11568. Eur. J. Pharmacol. 220:11–17

    Google Scholar 

  24. Min-Che Huang, J., Rian, H., Bacaner, M. 1992. Long-chain fatty acids activate calcium channels in ventricular myocytes. Proc. Natl. Acad. Sci. USA 89:6452–6456

    Google Scholar 

  25. Müller, M., Szewczyk, A., De Weille, J.R., Lazdunski, M. 1992. ATP-sensitive K+ channels in insulinoma cells are activated by non-esterified fatty acids. Biochemistry 31:4656–4661

    Google Scholar 

  26. Naor, Z., Shearman, M.S., Kishimoto, A., Nishizuka, Y. 1988. Calcium-indpendent activation of hypothalamic type I protein kinase C by unsaturated fatty acids. Mol. Endocrinol. 2:1043–1048

    Google Scholar 

  27. Norrdin, R.W., Jee, W.S.S., High, W.B. 1990. Review: the role of prostaglandins in bone in vivo. Prostaglandins Leukotrienes and Essential Fatty Acids 41:139–149

    Google Scholar 

  28. Ordway, R.W., Walsh, J.V., Singer, J.J. 1989. Arachidonic acid and other fatty acids directly activate potassium channels in smooth muscle cells. Science 244:1176–1179

    Google Scholar 

  29. Piomelli, D., Voltera, A., Dale, N., Siegelbaum, S.A., Kandel, E.R., Schwartz, J.H., Belardetti, F. 1987. Lipoxygenase metabolites of arachidonic acid as second messengers for presynaptic inhibition of Aplysia sensory cells. Nature 328:38–43

    Google Scholar 

  30. Piomelli, D., Greengard, P. 1990. Lipoxygenase metabolites of arachidonic acid in neural transmembrane signalling. Trends Physiol. Sci. 11:367–373

    Google Scholar 

  31. Premkumar, L.S., Gage, P.W., Chung, S.H. 1990. Coupled potassium channels induced by arachidonic acid in cultured neurons. Proc. R. Soc. Lond. B 242:17–22

    Google Scholar 

  32. Reich, K.M., Frangos, J.A. 1991. Effect of flow on prostaglandin E2 and inositol trisphosphate levels in osteoblasts. Am. J. Physiol. 261:C428-C432

    Google Scholar 

  33. Rouzaire-Dubois, B., Gérard, V., Dubois, J.M. 1991. Modification of K+ channel properties induced by fatty acids in neuroblastoma cells. Pfluegers Arch. 419:467–471

    Google Scholar 

  34. Scherübl, H., Hescheler, J. 1992. Transient membrane hyperpolarizations due to spontaneous fluctuations of the cytosolic Ca2+ in osteoblast-like cells. Pfluegers Arch. 420:109–111

    Google Scholar 

  35. Schweitzer, P., Madamba, S., Siggins, G.R. 1990. Arachidonic acid metabolites as mediators of somatostatin-induced increase of neuronal M-current. Nature 346:464–467

    Google Scholar 

  36. Shimada, T., Somlyo, A.P. 1992. Modulation of voltage-dependent Ca channel current by arachidonic acid and other longchain fatty acids in rabbit intestinal smooth muscle. J. Gen. Physiol. 100:27–44

    Google Scholar 

  37. Suarez, F., Silve, C. 1992. Effect of parathyroid hormone on arachidonic acid metabolism in mouse osteoblasts: permissive action of dexamethasone. Endocrinology 130:592–598

    Google Scholar 

  38. Tatakis, D.N., Schneeberger, G., Dziak, R. 1988. Recombinant interleukin-1 stimulates prostaglandin E2 production by osteoblastic cells: synergy with parathyroid hormone. Calcif. Tissue Int. 42:358–362

    Google Scholar 

  39. Vacher, P., McKenzie, J., Dufy, B. 1989. Arachidonic acid affects membrane ionic conductances of GH3 pituitary cells. Am J. Physiol. 257:E203-E211

    Google Scholar 

  40. Wallach, D., Pastan, I. 1976. Stimulation of guanylate cyclase of fibroblasts by free fatty acids. J. Biol. Chem. 251:5802–5809

    Google Scholar 

  41. Wang, W., Schwab, A., Giebisch, G. 1990. Regulation of smallconductance K+ channel in apical membrane of rat cortical collecting tubule. Am J. Physiol. 259:F494-F502

    Google Scholar 

  42. Wang, W., Cassola, A., Giebisch, G. 1992. Arachidonic acid inhibits the secretory K+ channel of cortical collecting duct of rat kidney. Am J. Physiol. 262:F554-F559

    Google Scholar 

  43. Ypey, D., Ravesloot, J., Buisman, M., Nijweide, P. 1988. Voltage-activated ionic channels and conductances in embryonic chick osteoblast cultures. J. Membrane Biol. 101:141–150

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

We wish to thank P. Ascher and J.S. Kehoe for helpful discussion and critical reading of the manuscript. We are very grateful to J. Pons for patient and expert secretarial assistance. This work was supported by the CNRS (URA 295, URA 583).

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chesnoy-Marchais, D., Fritsch, J. Concentration-dependent modulations of potassium and calcium currents of rat osteoblastic cells by arachidonic acid. J. Membarin Biol. 138, 159–170 (1994). https://doi.org/10.1007/BF00232644

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00232644

Key words

Navigation