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Chloride current activated by cyclic AMP and parathyroid hormone in rat osteoblasts

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Abstract

In primary cultures of rat osteoblasts, studied with the whole-cell configuration of the patch-clamp technique, 8-bromo-cyclic AMP (8BrcAMP) forskolin (FS) and 1–34 parathyroid hormone (PTH) were shown to activate a Cl conductance. This conductance shows a pronounced outward rectification, even with symmetrical Cl concentrations. It is blocked partially and reversibly by 4,4′-diisothiocyanatostilbene 2,2′-disulfonic acid (DIDS) or diphenylcarboxylate (DPC). The blockade induced by DIDS is time-and voltage-dependent. The Cl responses to FS and PTH develop slowly, after a delay of several seconds and are very slowly reversible. These responses were observed only in a fraction of the cells tested and their detection was favoured by cell dialysis. This Cl current should be taken into account for studying possible modulations of the voltage-gated Ca currents of osteoblasts. It is suggested that its physiological role may be related to the well-known morphological changes induced by PTH in osteoblasts. The cyclic AMP-sensitivity, the outward rectification and the sensitivity to dialysis of this Cl current are reminiscent of the properties of the cystic fibrosis-sensitive Cl channels of epithelial cells.

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References

  • Bean BP (1989) Classes of calcium channel in vertebrate cells. Annu Rev Physiol 51:367–384

    Google Scholar 

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

    Google Scholar 

  • Edelman A, Fritsch J, Balsan S (1986) Short-term effects of PTH on cultured rat osteoblasts: changes in membrane potential. Am J Physiol 251:C483–490

    Google Scholar 

  • Frizzell RA, Rechkemmer GR, Schoemaker RL (1986) Altered regulation of airway epithelial cell chloride channels in cystic fibrosis. Science 233:558–560

    Google Scholar 

  • Gray PTA, Ritchie JM (1986) A voltage-gated chloride conductance in rat cultured astrocytes. Proc R Soc Lond B 228:267–288

    Google Scholar 

  • Greger R, Schlatter E, Gögelein H (1985) Cl-channels in the apical cell membrane of the rectal gland “induced” by cAMP. Pflügers Arch 403:446–448

    Google Scholar 

  • Greger R, Schlatter E, Gögelein H (1987) Chloride channels in the luminal membrane of the rectal gland of the dogfish (Squalus acanthias). Properties of the ‘larger” conductance channel. Pflügers Arch 409:114–121

    Google Scholar 

  • Halm DR, Rechkemmer GR, Schoumacher RA, Frizzell RA (1988) Apical membrane chloride channels in a colonic cell line activated by secretory agonists. Am J Physiol 254:C505–511

    Google Scholar 

  • Hamill OP, Marty A, Neher E, Sakmann B, Sigworth FJ (1981) Improved patch-clamp technique for high-resolution current recording from cells and cell-free membrane patches. Pflügers Arch 391:85–100

    Google Scholar 

  • Hayslett JP, Gögelein H, Kunzelmann K, Greger R (1987) Characteristics of apical chloride channels in human colon cells (HT 29). Pflügers Arch 410:487–494

    Google Scholar 

  • Hymel L, Striessnig J, Glossmann H, Schindler H (1988) Purified skeletal muscle 1,4-dihydropyridine receptor forms phosphorylation-dependent oligomeric calcium channels in planar bilayers. Proc Natl Acad Sci USA 85:4290–4294

    Google Scholar 

  • Johnson JW, Ascher P (1987) Glycine potentiates the NMDA response in cultured mouse brain neurons. Nature 325:529–531

    Google Scholar 

  • Li M, McCann JD, Liedtke CM, Nairn AC, Greengard P, Welsh MJ (1988) Cyclic AMP-dependent protein kinase opens chloride channels in normal but not cystic fibrosis airway epithelium. Nature 331:358–360

    Google Scholar 

  • Lieberherr M (1987) Effects of vitamin D3 metabolites on cytosolic free calcium in confluent mouse osteoblasts. J Biol Chem 262:13168–13173

    Google Scholar 

  • Lindskog S, Blomlöf L, Hammarström L (1987) Comparative effects of parathyroid hormone on osteoblasts and cementoblasts. J Clin Periodontol 14:386–389

    Google Scholar 

  • Löwik CWGM, Van Leeuwen JPTM, Van der Meer J, Van Zeeland JK, Scheven BAA, Hermann-Erlee MPM (1985) A two-receptor model for the action of parathyroid hormone on osteoblast: a role for intracellular calcium and cAMP. Cell Calcium 6:311–326

    Google Scholar 

  • Ma J, Coronado R (1988) Heterogeneity of conductance states in calcium channels of skeletal muscle. Biophys J 53:387–395

    Google Scholar 

  • Palade PT, Barchi RL (1977) On the inhibition of muscle membrane chloride conductance by aromatic carboxylic acids. J Gen Physiol 69:879–896

    Google Scholar 

  • Penner R, Matthews G, Neher E (1988) Regulation of calcium influx by second messengers in rat mast cells. Nature 334:499–504

    Google Scholar 

  • Reid IR, Civitelli R, Halstead LR, Avioli LV, Hruska KA (1987) Parahyroid hormone acutely elevates intracellular calcium in osteoblast like cells. Am J Physiol 252:E45-E51

    Google Scholar 

  • Rodan GA, Rodan SB (1984) Expression of the osteoblastic phenotype. In: Peck WA (ed) Bone and mineral research, Annual 2. Elsevier, Amsterdam New York, pp 244–285

    Google Scholar 

  • Schoumacher RA, Shoemaker RL, Halm DR, Tallant EA, Wallace RW, Frizzell RA (1987) Phosphorylation fails to activate chloride channels from cystic fibrosis airway cells. Nature 330:752–754

    Google Scholar 

  • Ship S, Shami Y, Breuer W, Rothstein A (1977) Synthesis of tritiated 4,4′-diisothiocyano — 2,2′-stilbene disulfonic acid (3([H] DIDS) and its covalent reaction with sites related to anion transport in red blood cells. J Membr Biol 33:311–324

    Google Scholar 

  • Seamon KB, Padget W, Daly JW (1981) Forskolin: unique diterpene activator of adenylate cyclase in membranes and in intact cells. Proc Natl Acad Sci USA 78:3363–3367

    Google Scholar 

  • Van Leeuwen JPTM, Bos MP, Löwik CWGM, Hermann-Erlee MPM (1988) Effect of parathyroid hormone and parathyroid hormone fragments on the intracellular ionized calcium concentration in an osteoblast cell line. Bone and Mineral 4:177–188

    Google Scholar 

  • Wangemann P, Wittner M, Di Stefano A, Englert HC, Lang HJ, Schlatter E, Greger R (1986) Cl-channel blockers in the thick ascending limb of the loop of Henle. Structure activity relationship. Pflügers Arch 407 (Suppl 2):S128-S141

    Google Scholar 

  • Welsh MJ (1986) Single apical membrane anion channels in primary cultures of canine tracheal epithelium. Pflügers Arch 407 (Suppl 2): S116-S122

    Google Scholar 

  • Welsh MJ, Liedtke CM (1986) Chloride and potassium channels in cystic fibrosis airway epithelia. Nature 322:467–470

    Google Scholar 

  • Yamaguchi DT, Hahn TJ, Iida-Klein A, Kleeman CR, Muallem S (1987) Parathyroid hormone-activated calcium channels in an osteoblast-like clonal oesteosarcoma cell line. J Biol Chem 262:7711–7718

    Google Scholar 

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Chesnoy-Marchais, D., Fritsch, J. Chloride current activated by cyclic AMP and parathyroid hormone in rat osteoblasts. Pflugers Arch. 415, 104–114 (1989). https://doi.org/10.1007/BF00373147

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  • DOI: https://doi.org/10.1007/BF00373147

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