title: Density of functional Ca2+ release-activated Ca2+ (CRAC) channels declines after T-cell activation.
abstract: CRAC channel-mediated Ca(2+) entry plays a crucial role in T lymphocyte activation. Activated T cells display enhanced Ca(2+) signaling compared with resting T cells; this is partially attributed to activation-induced upregulation of CRAC channel expression. Orai and Stim family genes encode CRAC channel structural elements and regulatory proteins, respectively, but studies of their expression in T cells have led to controversial results. We re-examined Orai and Stim gene expression in resting, activated, and Jurkat T cells. Levels of Orai1 transcripts, encoding the human T cell CRAC channel subunit, were not significantly different between resting T and activated T cells. The total amount of all Orai transcripts was 2-fold higher in activated T cells than in resting T cells. Orai1 and total Orai transcript levels were significantly higher in Jurkat T cells than those in resting T cells. Stim expression did not vary significantly among cell types. Maximal whole-cell CRAC current amplitudes were 1.4-fold and 2.3-fold higher in activated and Jurkat T cells, respectively, than in resting T cells. Due to the small size of resting T cells, the surface CRAC channel density was 2.5-fold and 1.6-fold higher in resting T cells than in activated and Jurkat T cells, respectively. Predicted the rates of cytosolic Ca(2+) elevation calculated using the average values of CRAC channel currents and cell volumes showed that < 2-fold increase in the functional CRAC channel expression level cannot account for the enhanced rate of store-operated Ca(2+) entry in activated T cells compared with resting T cells.
authors.affiliation: University of California, Davis, USA.
authors.forename: Pratima
authors.initials: P
authors.lastname: Thakur
authors.forename: Alla F
authors.initials: AF
authors.lastname: Fomina
mesh_terms: D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000502:physiology*; D008297:Male; D000071740:ORAI1 Protein; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism*
chemical_list: D015220:Calcium Channels; D000071740:ORAI1 Protein; C510746:ORAI1 protein, human; D002118:Calcium