JCB logo
PeproTech: Free Shipping at www.peprotech.com
  Home | Help | Feedback | Subscriptions | Archive | Search | Search Results

*Download ALL Selected Citations
 to Citation Manager
Selected Abstracts
Returned: 1 citations and abstracts. Click on down arrow or scroll to see abstracts.

Down Alla F. Fomina, Christopher M. Fanger, J. Ashot Kozak, and Michael D. Cahalan
Single Channel Properties and Regulated Expression of Ca2+ Release-Activated Ca2+ (Crac) Channels in Human T Cells
J. Cell Biol., Sep 2000; 150: 1435 - 1444.


Abstract 1 of 1 Back
Alla F. Fomina, Christopher M. Fanger, J. Ashot Kozak, and Michael D. Cahalan
Single Channel Properties and Regulated Expression of Ca2+ Release-Activated Ca2+ (Crac) Channels in Human T Cells
J. Cell Biol., Sep 2000; 150: 1435 - 1444.

© The Rockefeller University Press, 0021-9525/2000//1435 $5.00
The Journal of Cell Biology, Volume 150, Number 6, , 2000 1435-1444


Original Article

Single Channel Properties and Regulated Expression of Ca2+ Release-Activated Ca2+ (Crac) Channels in Human T Cells



Alla F. Fominaa, Christopher M. Fangera, J. Ashot Kozaka, and Michael D. Cahalana

a Department of Physiology and Biophysics, University of California Irvine, Irvine, California 92697-4561
Department of Physiology and Biophysics, University of California Irvine, Irvine, CA 92697-4561.(949) 824-3143(949) 824-7776

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



© 2000 The Rockefeller University Press

Abbreviations used in this paper: BAPTA, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; [Ca2+]i, intracellular calcium concentration; CRAC, Ca2+ release-activated Ca2+; CsA, cyclosporin A; HEDTA, N-hydroxyethyl-ethylenediamine-triacetic acid; KCa, Ca2+-activated K+; NF-AT, nuclear factor of activated T cells; NMDG+, N-methyl D-glucamine; PHA, phytohemagglutinin; TCR, T cell receptor; Tg, thapsigargin.


[Full Text] [Reprint (PDF) Version]

  Home | Help | Feedback | Subscriptions | Archive | Search | Search Results