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J. Biol. Chem., Vol. 276, Issue 15, 12249-12256, April 13, 2001
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From the 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 KCa 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 Ca2+ signaling.
Calcium-activated Potassium Channels Sustain Calcium Signaling in
T Lymphocytes
SELECTIVE BLOCKERS AND MANIPULATED CHANNEL EXPRESSION
LEVELS*
§,,,
,,, and
Department of Physiology and Biophysics,
University of California, Irvine, California 92697-4561, ¶ 4SC
AG Drug Discovery, 82152 Martinsried, Germany, A. Bernauer
Strasse, 80687 München, Germany, and the ** Department of
Chemistry, University College London, 20 Gordon Street,
London WC1H OAJ, England
*
This work was supported by National Institutes of Health
Grants NS14609 and GM41514 (to M. D. C.), National Institutes of Health Grants MH59222 and GM54221 (to K. G. C.), a Feodor Lynen fellowship from the Alexander von Humboldt Foundation (to H. R.), and
Deutsche Forschungsgemeinschaft Fellowship Grant WU 320/1-1 and
Western States Affiliate of the American Heart Association Grant
9920014Y (to H. W.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed. Tel.: 949-824-7776;
Fax: 949-824-3143; E-mail: mcahalan@uci.edu.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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