Single channel properties and regulated expression of Ca2+ release-activated Ca2+ (CRAC) channels in human T cells

Alla F Fomina, C. M. Fanger, J. A. Kozak, M. D. Cahalan

Research output: Contribution to journalArticle

85 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1435-1444
Number of pages10
JournalJournal of Cell Biology
Volume150
Issue number6
DOIs
StatePublished - Sep 18 2000

Keywords

  • Ca channel
  • Ca signaling
  • CRAC channel
  • T cell activation
  • T lymphocyte

ASJC Scopus subject areas

  • Cell Biology

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