Calcium oscillations in T-cells: mechanisms and consequences for gene expression

Abstract

[Ca(2+)](i) (intracellular Ca(2+) concentration) oscillations play a central role in the activation of T-lymphocytes by antigen. Oscillations in T-cells are absolutely dependent on Ca(2+) influx through store-operated CRAC channels (Ca(2+)-release-activated Ca(2+) channels), and evidence suggests that they arise from delayed interactions between these channels and Ca(2+) stores. Their potential functions have been explored by creating controlled [Ca(2+)](i) oscillations with pulses of Ca(2+) entry or pulses of Ins(1,4,5)P(3). Oscillations enhance both the efficiency and specificity of signalling through the Ca(2+)-dependent transcription factors nuclear factor of activated T-cells (NFAT), Oct/Oap and nuclear factor kappa B (NF kappa B) in ways that are consistent with each factor's Ca(2+) dependence and kinetics of activation and deactivation. These studies show how [Ca(2+)](i) oscillations may enhance signalling to the nucleus, and suggest a possible cellular mechanism for extracting information encoded in oscillation frequency.