Mitogen-Regulated Ca2+Current of T Lymphocytes is Activated by Depletion of Intracellular Ca2+Stores
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 ge...
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Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 1993-07, Vol.90 (13), p.6295-6299 |
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Zusammenfassung: | 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 Ca2+-ATPase inhibitor that depletes intracellular stores without generating IP3. Both currents are blocked by Ni2+, are inwardly rectifying, are highly Ca2+-selective, and exhibit voltage-independent gating with a unitary chord conductance of ≈24 fS in isotonic Ca2+. Fluctuation analysis suggests that the underlying Ca2+transporter is a channel rather than an ion carrier. Thus, in terms of ion permeation, gating, and unitary conductance, the Ca2+current activated by thapsigargin is indistinguishable from that elicited by crosslinking of T-cell receptors. Moreover, the unitary Ca2+conductance is >100-fold smaller than that of previously described IP3-gated, Ca2+-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 IP3on Ca2+channels in the plasma membrane. |
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ISSN: | 0027-8424 1091-6490 |
DOI: | 10.1073/pnas.90.13.6295 |