Mitogen-regulated Ca2+ current of T lymphocytes is activated by depletion of intracellular Ca2+ stores.
Mitogen-regulated Ca2+ current of T lymphocytes is activated by depletion of intracellular Ca2+ stores.
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DOI：
10.1073/pnas.90.13.6295
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发表时间：
1993-07
影响因子：
11.1
通讯作者：
A. Zweifach;R. Lewis
中科院分区：
文献类型：
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作者：
A. Zweifach;R. Lewis
受刺激的Ca 2+跨T淋巴细胞质膜内流是抗原激活T细胞的重要触发信号。T细胞钙离子电导的调节尚不清楚;相互矛盾的证据支持直接激活肌醇1，4，5-三磷酸（IP 3）或细胞内钙储存耗尽产生的信号。我们使用穿孔膜片记录技术比较了由T细胞受体刺激和毒胡萝卜素激活的Ca 2+电流的生物物理特性，毒胡萝卜素是一种Ca（2+）-ATP酶抑制剂，消耗细胞内储存而不产生IP 3。这两种电流都被Ni 2+阻断，是向内整流的，是高度Ca（2+）选择性的，并且在等渗Ca 2+中表现出电压无关的门控，具有约24 fS的单位弦电导。波动分析表明，潜在的Ca 2+转运蛋白是一个通道，而不是一个铁载体。因此，在离子渗透、门控和单位电导方面，由毒胡萝卜素激活的Ca 2+电流与由T细胞受体交联引起的电流是不可区分的。此外，单位Ca 2+电导比先前描述的T细胞中IP 3门控的Ca（2+）可渗透通道的电导小> 100倍[Kuno，M.和Gardner，P.（1987）Nature（伦敦）326，301-304]。这些结果表明，丝裂原激活的Ca 2+内流是由胞内Ca 2+储存的状态控制，而不是由IP 3对质膜中Ca 2+通道的直接作用。
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.