Kotturi Maya F, Hunt Simon V, Jefferies Wilfred A
The Biomedical Research Centre, Michael Smith Laboratories, University of British Columbia, 2222 Health Sciences Mall, Vancouver, BC, Canada.
Trends Pharmacol Sci. 2006 Jul;27(7):360-7. doi: 10.1016/j.tips.2006.05.007.
Ca2+ channels in the plasma membrane of T cells vitally influence Ca2+-dependent signals that lead ultimately to cytokine secretion, cellular proliferation and apoptosis. Conventional models depict the Ca2+ inrush across the T-cell membrane following T-cell receptor engagement as being due to Ca2+-release-activated Ca2+ (CRAC) channels. A poorly understood mechanism detects the lowered Ca2+ concentrations within intracellular stores that open CRAC channels. Mammalian homologs of the Drosophila transient receptor potential Ca2+ channels possibly help to gate the store-operated, Ca2+-borne CRAC current. In this article, we review evidence of a supplementary involvement of other Ca2+ channels, the opening of which does not necessarily reflect intracellular Ca2+-store depletion. We highlight a role for variants of L-type voltage-dependent Ca2+ channels in increasing intracellular Ca2+ concentrations during activation. For more-accurate modeling of lymphocyte activation and possible pharmacological interventions, future research should aim to identify physiologically relevant situations in which such channels help to shape the Ca2+ signal.
T细胞膜中的钙离子通道对钙离子依赖信号起着至关重要的作用，这些信号最终会导致细胞因子分泌、细胞增殖和凋亡。传统模型认为，T细胞受体激活后，钙离子涌入T细胞膜是由钙离子释放激活的钙离子（CRAC）通道引起的。一种尚未完全了解的机制能够检测细胞内储存库中降低的钙离子浓度，从而开启CRAC通道。果蝇瞬时受体电位钙离子通道的哺乳动物同源物可能有助于调控储存库操纵的钙离子携带的CRAC电流。在本文中，我们回顾了其他钙离子通道可能起到补充作用的证据，这些通道的开放不一定反映细胞内钙离子储存库的耗竭。我们强调了L型电压依赖性钙离子通道变体在激活过程中增加细胞内钙离子浓度方面的作用。为了更准确地模拟淋巴细胞激活以及可能的药物干预，未来的研究应致力于确定这些通道有助于塑造钙离子信号的生理相关情况。
