Abstract
1. Stimulation of mast cells by externally applied secretagogues activated a slowly developing membrane current. With high external and low internal chloride (Cl-) concentrations, the current reversed at about -40 mV, but when external Cl- was made equal to internal Cl-, the reversal potential shifted to about 0 mV, demonstrating that the current carrier was Cl-. 2. In addition to external agonists, internally applied cyclic AMP and high concentrations of intracellular calcium [Ca2+]i could also activate the Cl- current. However, elevated [Ca2+]i produced only slow and incomplete activation. This suggests that the Cl- current is not directly Ca2+ activated. Also, activation of Cl- current by external agonists and by cyclic AMP was unimpaired when [Ca2+]i was clamped to low levels with internal ethylene glycol bis-N,N,N',N'-tetraacetic acid (EGTA), indicating that elevated [Ca2+]i is not necessary for activation of the Cl- current. Although activation by cyclic AMP was faster than that produced by elevated [Ca2+]i, it still required tens of seconds; thus the effect of cyclic AMP was also likely to be indirect. 3. Internal guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma-S) could also activate the Cl- current, suggesting the involvement of a G protein in the control of the current. 4. The variance associated with the Cl- current was small, and noise analysis gave a lower limit of about 1-2 pS for the single-channel conductance. The Cl- current was reduced by 4,4'-diisothiocyano-2,2'-stilbenedisulphonate (DIDS), and during DIDS blockade, the variance of the current increased. This suggests that DIDS enters and blocks the open channel. 5. Activation of the Cl- current would make the membrane potential negative following stimulation of a mast cell, thus providing a driving force for entry of external calcium via the stimulation-induced influx pathways described in the preceding paper (Matthews, Neher & Penner, 1989).
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Selected References
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- Beaven M. A., Moore J. P., Smith G. A., Hesketh T. R., Metcalfe J. C. The calcium signal and phosphatidylinositol breakdown in 2H3 cells. J Biol Chem. 1984 Jun 10;259(11):7137–7142. [PubMed] [Google Scholar]
- Cahalan M. D., Lewis R. S. Role of potassium and chloride channels in volume regulation by T lymphocytes. Soc Gen Physiol Ser. 1988;43:281–301. [PubMed] [Google Scholar]
- Claret M., Mazet J. L. Ionic fluxes and permeabilities of cell membranes in rat liver. J Physiol. 1972 Jun;223(2):279–295. doi: 10.1113/jphysiol.1972.sp009847. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Di Virgilio F., Lew P. D., Andersson T., Pozzan T. Plasma membrane potential modulates chemotactic peptide-stimulated cytosolic free Ca2+ changes in human neutrophils. J Biol Chem. 1987 Apr 5;262(10):4574–4579. [PubMed] [Google Scholar]
- Hayslett J. P., Gögelein H., Kunzelmann K., Greger R. Characteristics of apical chloride channels in human colon cells (HT29). Pflugers Arch. 1987 Nov;410(4-5):487–494. doi: 10.1007/BF00586530. [DOI] [PubMed] [Google Scholar]
- Hazama A., Okada Y. Ca2+ sensitivity of volume-regulatory K+ and Cl- channels in cultured human epithelial cells. J Physiol. 1988 Aug;402:687–702. doi: 10.1113/jphysiol.1988.sp017229. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Latorre R., Miller C. Conduction and selectivity in potassium channels. J Membr Biol. 1983;71(1-2):11–30. doi: 10.1007/BF01870671. [DOI] [PubMed] [Google Scholar]
- Marty A., Evans M. G., Tan Y. P., Trautmann A. Muscarinic response in rat lacrimal glands. J Exp Biol. 1986 Sep;124:15–32. doi: 10.1242/jeb.124.1.15. [DOI] [PubMed] [Google Scholar]
- Matthews G., Neher E., Penner R. Second messenger-activated calcium influx in rat peritoneal mast cells. J Physiol. 1989 Nov;418:105–130. doi: 10.1113/jphysiol.1989.sp017830. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McPherson M. A., Dormer R. L. Cystic fibrosis: a defect in stimulus-response coupling. Trends Biochem Sci. 1988 Jan;13(1):10–13. doi: 10.1016/0968-0004(88)90010-2. [DOI] [PubMed] [Google Scholar]
- Meech R. W. Calcium-dependent potassium activation in nervous tissues. Annu Rev Biophys Bioeng. 1978;7:1–18. doi: 10.1146/annurev.bb.07.060178.000245. [DOI] [PubMed] [Google Scholar]
- Miller C., White M. M. Dimeric structure of single chloride channels from Torpedo electroplax. Proc Natl Acad Sci U S A. 1984 May;81(9):2772–2775. doi: 10.1073/pnas.81.9.2772. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mohr F. C., Fewtrell C. The relative contributions of extracellular and intracellular calcium to secretion from tumor mast cells. Multiple effects of the proton ionophore carbonyl cyanide m-chlorophenylhydrazone. J Biol Chem. 1987 Aug 5;262(22):10638–10643. [PubMed] [Google Scholar]
- Neher E., Almers W. Fast calcium transients in rat peritoneal mast cells are not sufficient to trigger exocytosis. EMBO J. 1986 Jan;5(1):51–53. doi: 10.1002/j.1460-2075.1986.tb04176.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Neher E. The influence of intracellular calcium concentration on degranulation of dialysed mast cells from rat peritoneum. J Physiol. 1988 Jan;395:193–214. doi: 10.1113/jphysiol.1988.sp016914. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Oettgen H. C., Terhorst C., Cantley L. C., Rosoff P. M. Stimulation of the T3-T cell receptor complex induces a membrane-potential-sensitive calcium influx. Cell. 1985 Mar;40(3):583–590. doi: 10.1016/0092-8674(85)90206-5. [DOI] [PubMed] [Google Scholar]
- Penner R., Matthews G., Neher E. Regulation of calcium influx by second messengers in rat mast cells. Nature. 1988 Aug 11;334(6182):499–504. doi: 10.1038/334499a0. [DOI] [PubMed] [Google Scholar]
- Penner R. Multiple signaling pathways control stimulus-secretion coupling in rat peritoneal mast cells. Proc Natl Acad Sci U S A. 1988 Dec;85(24):9856–9860. doi: 10.1073/pnas.85.24.9856. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Penner R., Pusch M., Neher E. Washout phenomena in dialyzed mast cells allow discrimination of different steps in stimulus-secretion coupling. Biosci Rep. 1987 Apr;7(4):313–321. doi: 10.1007/BF01121453. [DOI] [PubMed] [Google Scholar]
- Sage S. O., Rink T. J. Effects of ionic substitution on [Ca2+]i rises evoked by thrombin and PAF in human platelets. Eur J Pharmacol. 1986 Aug 22;128(1-2):99–107. doi: 10.1016/0014-2999(86)90563-7. [DOI] [PubMed] [Google Scholar]
- Sullivan T. J., Parker K. L., Eisen S. A., Parker C. W. Modulation of cyclic AMP in purified rat mast cells. II. Studies on the relationship between intracellular cyclic AMP concentrations and histamine release. J Immunol. 1975 May;114(5):1480–1485. [PubMed] [Google Scholar]
- Takahashi T., Neher E., Sakmann B. Rat brain serotonin receptors in Xenopus oocytes are coupled by intracellular calcium to endogenous channels. Proc Natl Acad Sci U S A. 1987 Jul;84(14):5063–5067. doi: 10.1073/pnas.84.14.5063. [DOI] [PMC free article] [PubMed] [Google Scholar]
