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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1993 Jul 1;90(13):6295–6299. doi: 10.1073/pnas.90.13.6295

Mitogen-regulated Ca2+ current of T lymphocytes is activated by depletion of intracellular Ca2+ stores.

A Zweifach 1, R S Lewis 1
PMCID: PMC46915  PMID: 8392195

Abstract

Stimulated influx of Ca2+ across the plasma membrane of T lymphocytes is an essential triggering signal for T-cell activation by antigen. Regulation of the T-cell Ca2+ conductance is not understood; conflicting evidence supports direct activation by inositol 1,4,5-trisphosphate (IP3) or by a signal generated by the depletion of intracellular Ca2+ stores. We have used the perforated-patch recording technique to compare the biophysical properties of Ca2+ currents activated by T-cell receptor stimulation and by thapsigargin, a Ca(2+)-ATPase inhibitor that depletes intracellular stores without generating IP3. Both currents are blocked by Ni2+, are inwardly rectifying, are highly Ca(2+)-selective, and exhibit voltage-independent gating with a unitary chord conductance of approximately 24 fS in isotonic Ca2+. Fluctuation analysis suggests that the underlying Ca2+ transporter is a channel rather than an iron carrier. Thus, in terms of ion permeation, gating, and unitary conductance, the Ca2+ current activated by thapsigargin is indistinguishable from the elicited by crosslinking of T-cell receptors. Moreover, the unitary Ca2+ conductance is > 100-fold smaller than that of previously described IP3-gated, Ca(2+)-permeable channels in T cells [Kuno, M. & Gardner, P. (1987) Nature (London) 326, 301-304]. These results demonstrate that mitogen-activated Ca2+ influx is controlled by the state of intracellular Ca2+ stores rather than by the direct action of IP3 on Ca2+ channels in the plasma membrane.

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Selected References

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