Calcium-activated potassium channels sustain calcium signaling in T lymphocytes. Selective blockers and manipulated channel expression levels.
To maintain Ca(2+) entry during T lymphocyte activation, a balancing efflux of cations is necessary. Using three approaches, we demonstrate that this cation efflux is mediated by Ca(2+)-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 Ca(2+) 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 Ca(2+) influx. Finally, introduction of the hIKCa1 channel into Jurkat T cells maintains rapid Ca(2+) 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.
Department of Physiology and Biophysics, University of California, Irvine, California 92697-4561, USA.
C M
CM
Fanger
H
H
Rauer
A L
AL
Neben
M J
MJ
Miller
H
H
Rauer
H
H
Wulff
J C
JC
Rosa
C R
CR
Ganellin
K G
KG
Chandy
M D
MD
Cahalan
D000818:Animals; D019556:COS Cells; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D006801:Humans; D019169:Jurkat Cells; D015221:Potassium Channels / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*
D015221:Potassium Channels; D002118:Calcium