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Original Article |
Correspondence to: Michael D. Cahalan, Department of Physiology and Biophysics, University of California Irvine, Irvine, CA 92697-4561. Tel:(949) 824-7776 Fax:(949) 824-3143
Although the crucial role of Ca2+ influx in lymphocyte activation has been well documented, little is known about the properties or expression levels of Ca2+ channels in normal human T lymphocytes. The use of Na+ as the permeant ion in divalent-free solution permitted Ca2+ release-activated Ca2+ (CRAC) channel activation, kinetic properties, and functional expression levels to be investigated with single channel resolution in resting and phytohemagglutinin (PHA)-activated human T cells. Passive Ca2+ store depletion resulted in the opening of 41-pS CRAC channels characterized by high open probabilities, voltage-dependent block by extracellular Ca2+ in the micromolar range, selective Ca2+ permeation in the millimolar range, and inactivation that depended upon intracellular Mg2+ ions. The number of CRAC channels per cell increased greatly from
15 in resting T cells to
140 in activated T cells. Treatment with the phorbol ester PMA also increased CRAC channel expression to
60 channels per cell, whereas the immunosuppressive drug cyclosporin A (1 µM) suppressed the PHA-induced increase in functional channel expression. Capacitative Ca2+ influx induced by thapsigargin was also significantly enhanced in activated T cells. We conclude that a surprisingly low number of CRAC channels are sufficient to mediate Ca2+ influx in human resting T cells, and that the expression of CRAC channels increases
10-fold during activation, resulting in enhanced Ca2+ signaling.
Key Words: T lymphocyte, Ca2+ channel, CRAC channel, T cell activation, Ca2+ signaling
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