Regulation of Calcium Entry Pathway in Jurkat T Cells

by Fruasaha, Petronilla A.

Calcium release-activated calcium channels (CRAC) control influx of calcium in human T lymphocytes. Hour-long calcium elevations are necessary for efficient gene expression during T cell activation and proliferation. We report here that, the time course for store-operated Ca2+ entry is short-lived (3-4 min) and therefore, cannot account for the prolonged Ca2+ elevations necessary for NFAT translocation into nucleus. Previous findings strongly suggest that T cell activation is accompanied by cytosolic alkalinization. Here, we show that pH changes in Jurkat T cells following activation with mitogenic lectin, phytohemagglutinin (PHA), depends on the length of time of exposure and the concentration (potency) of the mitogen. For full understanding of ion fluxes involved in this process, it is important to distinguish CRAC channel subtype functions in these cells during activation as well as elucidate the pH mediated changes in Ca2+. In some experiments we show low pH with high concentrations of PHA. We also investigated the dependence of 2-APB action on intracellular pH and show that it mediates its effect by acidification but consistently inhibits CRAC with NH4+-induced alkalinization. Finally, we showed that in agreement with a previous study, PIP3 specifically, can elicit calcium elevations in Jurkat T cells.