Pool depletion induces a novel calcium influx pathway activated by caffeine

C. A. Ufret-Vincenty, A. Alfpnso, D. Gill

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Co2+ influx through store-operated channels (SOCs) activated rapidly after Ca2+ pool depletion represents an important component of Ca2+ signals generated in cells. A new and distinct Ca2+ influx component activated by caffeine is induced in cells after Ca2+ pools are emptied using the intracellular Ca2+ pump inhibitors, thapsigargin (TG) or 2,5-di-fert- butylhydroquinone (DBHQ). Both blockers cause depletion of intracellular Ca2+ pools and eel! growth arrest; upon refilling of pools, normal cell-cycle progression is resumed (Short, A.D., et al. PNAS 90, 4986-4990, 1993). Here, the Co2+-sensitive dye, fura-2, was used to study Co2+ homeostasis in DDTMF - 2 smooth muscle cells growth-arrested by TG- or DBHQ-treatment. In DDTMF - 2 cells the SOC-mediated Ca2+ influx component after emptying Ca2+ pools is short- lived and appears to be rapidly deactivated. After treatment of DDTiMF - 2 cells with either 3 M TG or 10 /zM DBHQ, 10 mM caffeine induces a large transient influx of Ca2+ distinct from SOC- mediated Ca2+ entry. Caffeine-sensitive Ca2+ influx following DBHQ-treatment is activated more rapidly than that following TG-treatment. When caffeine is added to untreated DDT\MF - 2 cells no effect on cytosolic Co2+ concentration is observed. The disappearance of caffeine-induced Ca2+ influx is also different for TG- and DBHQ-treated cells. In DBHQ-treated cells, bradykinin- sensitive Ca2+ pools quickly refill and cells become insensitive to caffeine immediately after DBHQ removal. In the case of TG-Ueated cells, reversal of TG-induced growth arrest with either high (20%) serum or 1-10 /iM arachidonic acid, in addition to removal of TG, is required to allow agonist-sensitive Ca2+ pools to refill concomitantly with the disappearance of caffeine-induced Ca2+ influx. In summary, the results show that a Cu2+ influx pathway activated by caffeine is observed under conditions of growth arrest induced by either TG or DBHQ and appears to be directly correlated with depletion of intracellular Ca2+ pools. (NIH grants NS19304 and GM15407; NSF grant MCB 9307746).

Original languageEnglish (US)
Pages (from-to)A1373
JournalFASEB Journal
Issue number6
StatePublished - 1996

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics


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