To maintain Ca2+ entry during T lymphocyte activation, a balancing efflux of cations is necessary. Using three approaches, we demonstrate that this cation efflux is mediated by Ca2+-activated K+ (KCa) channels, hSKCa2 in the human leukemic T cell line Jurkat and hIKCa1 in mitogen-activated human T cells. First, several recently developed, selective and potent pharmacological inhibitors of K Ca channels but not KV channels reduce Ca2+ entry in Jurkat and in mitogen-activated human T cells. Second, dominant-negative suppression of the native KCa channel in Jurkat T cells by overexpression of a truncated fragment of the cloned hSKCa2 channel decreases Ca2+ influx. Finally, introduction of the hIKCa1 channel into Jurkat T cells maintains rapid Ca2+ entry despite pharmacological inhibition of the native small conductance KCa channel. Thus, KCa channels play a vital role in T cell Ca 2+ signaling.
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