Skip to main content
The Journal of Physiology logoLink to The Journal of Physiology
. 1996 Sep 1;495(Pt 2):331–338. doi: 10.1113/jphysiol.1996.sp021597

Differentiation of the human monocytic cell line U937 results in an upregulation of the calcium release-activated current, ICRAC.

R A Floto 1, M P Mahaut-Smith 1, J M Allen 1, B Somasundaram 1
PMCID: PMC1160795  PMID: 8887747

Abstract

1. Single cell fura-2 fluorescence measurements and whole-cell patch clamp recordings were used to investigate the effects of macrophage-like differentiation, induced by dibutyryl cAMP (dbcAMP), on Ca2+ influx triggered by Ca2+ store depletion in the human monocytic cell line, U937. 2. In differentiated cells, the rise in intracellular [Ca2+] following store depletion by thapsigargin (TG) in nominally Ca(2+)-free solution was 94% greater and the [Ca2+]i rise on subsequent re-addition of external Ca2+ (2 mM) was 292% greater than in undifferentiated cells. 3. Under conditions where [Ca2+]i was buffered by BAPTA, TG-induced store depletion failed to activate a detectable inward Ca2+ current in undifferentiated U937 cells. Under identical conditions, store depletion of differentiated U937 cells generated an inwardly rectifying Ca(2+)-selective current which showed no reversal from -140 to +30 mV and was blocked by 1 microM external La3+; characteristics of the calcium release-activated Ca2+ current (ICRAC) identified in other cells. 4. We conclude that U937 cells show a differentiation-dependent upregulation of a store-mediated Ca2+ entry pathway, identified as ICRAC, which is not correlated with the small associated increase in the size of TG-sensitive Ca2+ pools.

Full text

PDF
334

Selected References

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

  1. Balsinde J., Mollinedo F. Platelet-activating factor synergizes with phorbol myristate acetate in activating phospholipase D in the human promonocytic cell line U937. Evidence for different mechanisms of activation. J Biol Chem. 1991 Oct 5;266(28):18726–18730. [PubMed] [Google Scholar]
  2. Davis W., Halliwell E. L., Sage S. O., Allen J. M. Increased capacity for store regulated calcium influx in U937 cells differentiated by treatment with dibutyryl cAMP. Cell Calcium. 1995 May;17(5):345–353. doi: 10.1016/0143-4160(95)90108-6. [DOI] [PubMed] [Google Scholar]
  3. Dolmetsch R. E., Lewis R. S. Signaling between intracellular Ca2+ stores and depletion-activated Ca2+ channels generates [Ca2+]i oscillations in T lymphocytes. J Gen Physiol. 1994 Mar;103(3):365–388. doi: 10.1085/jgp.103.3.365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Fanger C. M., Hoth M., Crabtree G. R., Lewis R. S. Characterization of T cell mutants with defects in capacitative calcium entry: genetic evidence for the physiological roles of CRAC channels. J Cell Biol. 1995 Nov;131(3):655–667. doi: 10.1083/jcb.131.3.655. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Fasolato C., Innocenti B., Pozzan T. Receptor-activated Ca2+ influx: how many mechanisms for how many channels? Trends Pharmacol Sci. 1994 Mar;15(3):77–83. doi: 10.1016/0165-6147(94)90282-8. [DOI] [PubMed] [Google Scholar]
  6. Goldsmith M. A., Weiss A. Early signal transduction by the antigen receptor without commitment to T cell activation. Science. 1988 May 20;240(4855):1029–1031. doi: 10.1126/science.3259335. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Harris P., Ralph P. Human leukemic models of myelomonocytic development: a review of the HL-60 and U937 cell lines. J Leukoc Biol. 1985 Apr;37(4):407–422. doi: 10.1002/jlb.37.4.407. [DOI] [PubMed] [Google Scholar]
  9. Hoth M., Penner R. Depletion of intracellular calcium stores activates a calcium current in mast cells. Nature. 1992 Jan 23;355(6358):353–356. doi: 10.1038/355353a0. [DOI] [PubMed] [Google Scholar]
  10. Larsen N. E., Enelow R. I., Simons E. R., Sullivan R. Effect of bacterial endotoxin on the transmembrane electrical potential and plasma membrane fluidity of human monocytes. Biochim Biophys Acta. 1985 Apr 26;815(1):1–8. doi: 10.1016/0005-2736(85)90466-3. [DOI] [PubMed] [Google Scholar]
  11. Partiseti M., Le Deist F., Hivroz C., Fischer A., Korn H., Choquet D. The calcium current activated by T cell receptor and store depletion in human lymphocytes is absent in a primary immunodeficiency. J Biol Chem. 1994 Dec 23;269(51):32327–32335. [PubMed] [Google Scholar]
  12. Preston S. F., Sha'afi R. I., Berlin R. D. Regulation of Ca2+ influx during mitosis: Ca2+ influx and depletion of intracellular Ca2+ stores are coupled in interphase but not mitosis. Cell Regul. 1991 Nov;2(11):915–925. doi: 10.1091/mbc.2.11.915. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Putney J. W., Jr A model for receptor-regulated calcium entry. Cell Calcium. 1986 Feb;7(1):1–12. doi: 10.1016/0143-4160(86)90026-6. [DOI] [PubMed] [Google Scholar]
  14. Sargeant P., Sage S. O. Calcium signalling in platelets and other nonexcitable cells. Pharmacol Ther. 1994;64(3):395–443. doi: 10.1016/0163-7258(94)90019-1. [DOI] [PubMed] [Google Scholar]
  15. Serafini A. T., Lewis R. S., Clipstone N. A., Bram R. J., Fanger C., Fiering S., Herzenberg L. A., Crabtree G. R. Isolation of mutant T lymphocytes with defects in capacitative calcium entry. Immunity. 1995 Aug;3(2):239–250. doi: 10.1016/1074-7613(95)90093-4. [DOI] [PubMed] [Google Scholar]
  16. Sheth B., Dransfield I., Partridge L. J., Barker M. D., Burton D. R. Dibutyryl cyclic AMP stimulation of a monocyte-like cell line, U937: a model for monocyte chemotaxis and Fc receptor-related functions. Immunology. 1988 Mar;63(3):483–490. [PMC free article] [PubMed] [Google Scholar]
  17. Somasundaram B., Mahaut-Smith M. P. Three cation influx currents activated by purinergic receptor stimulation in rat megakaryocytes. J Physiol. 1994 Oct 15;480(Pt 2):225–231. doi: 10.1113/jphysiol.1994.sp020355. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Zweifach A., Lewis R. S. Mitogen-regulated Ca2+ current of T lymphocytes is activated by depletion of intracellular Ca2+ stores. Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6295–6299. doi: 10.1073/pnas.90.13.6295. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Zweifach A., Lewis R. S. Rapid inactivation of depletion-activated calcium current (ICRAC) due to local calcium feedback. J Gen Physiol. 1995 Feb;105(2):209–226. doi: 10.1085/jgp.105.2.209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Zweifach A., Lewis R. S. Slow calcium-dependent inactivation of depletion-activated calcium current. Store-dependent and -independent mechanisms. J Biol Chem. 1995 Jun 16;270(24):14445–14451. doi: 10.1074/jbc.270.24.14445. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Physiology are provided here courtesy of The Physiological Society

RESOURCES