Calcium-activated potassium channels sustain calcium signaling in T lymphocytes. Selective blockers and manipulated channel expression levels

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⁺ (K_Ca) 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 K_V channels reduce Ca²⁺ entry in Jurkat and in mitogen-activated human T cells. Second, dominant-negative suppression of the native K_Ca 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 K_Ca channel. Thus, K_Ca channels play a vital role in T cell Ca ²⁺ signaling.