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.
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Amagai, Y., Kasai, S. 1989. A voltage-dependent calcium current in mouse MC3T3-E1 osteogenic cells. Jap. J. Physiol. 39:773–777
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
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
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
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
Chesnoy-Marchais, D., Fritsch, J. 1988. Voltage-gated sodium and calcium currents in rat osteoblasts. J. Physiol. 398:291–311
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
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
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
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
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
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
Grygorczyk, C., Grygorczyk, R., Ferrier, J. 1989. Osteoblastic cells have L-type calcium channels. Bone and Mineral 7:137–148
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
Keyser, D.O., Alger, B.E. 1990. Arachidonic acid modulates hippocampal calcium current via protein kinase C and oxygen radicals. Neuron 5:545–553
Kim, D., Clapham, D.E. 1989. Potassium channels in cardiac cells activated by arachidonic acid and phospholipids. Science 244:1174–1176
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
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
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
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
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
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
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
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
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
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
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
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
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
Piomelli, D., Greengard, P. 1990. Lipoxygenase metabolites of arachidonic acid in neural transmembrane signalling. Trends Physiol. Sci. 11:367–373
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
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
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
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
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
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
Suarez, F., Silve, C. 1992. Effect of parathyroid hormone on arachidonic acid metabolism in mouse osteoblasts: permissive action of dexamethasone. Endocrinology 130:592–598
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
Vacher, P., McKenzie, J., Dufy, B. 1989. Arachidonic acid affects membrane ionic conductances of GH3 pituitary cells. Am J. Physiol. 257:E203-E211
Wallach, D., Pastan, I. 1976. Stimulation of guanylate cyclase of fibroblasts by free fatty acids. J. Biol. Chem. 251:5802–5809
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
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
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
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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).
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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
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DOI: https://doi.org/10.1007/BF00232644