Modulation of Ca2+ signaling by Na+/Ca2+ exchangers in mast cells
Modulation of Ca2+ signaling by Na+/Ca2+ exchangers in mast cells
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DOI：
10.4049/jimmunol.174.1.119
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发表时间：
2005-01-01
影响因子：
4.4
通讯作者：
Cavalié, A
中科院分区：
文献类型：
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作者：
Aneiros, E;Philipp, S;Cavalié, A
肥大细胞依靠 Ca2+ 信号传导来启动激活程序，从而释放促炎介质。内部钙池释放的 Ca2+ 与通过钙池操作的 Ca2+ 通道进入的 Ca2+ 之间的相互作用已得到广泛研究。使用大鼠嗜碱性白血病 (RBL) 肥大细胞和鼠骨髓来源的肥大细胞，我们研究了 Na+/Ca2+ 交换器的作用。钙成像实验和膜片钳电流记录揭示了 Na+/Ca2+ 交换的 K+ 独立成分和 K+ 依赖成分。 Northern 印迹分析表明 K+ 依赖性钠钙交换剂 NCKX3 的主要表达。另外通过 RT-PCR 在 RBL 细胞中检测到交换器 NCX3 和 NCKX1 的转录物。当Ca2+信号达到大于或等于200nM的水平时，通过Na+/Ca2+交换的Ca2+清除率相当于总清除率的50%。通过反转 Na+/Ca2+ 交换方向，Ca2+ 信号传导和钙池操作的 Ca2+ 进入大大减少，表明 Na+/Ca2+ 交换器通常从细胞质中挤出 Ca2+ 离子，并防止钙池操作的 Ca2+ 通道的 Ca2+ 依赖性失活。因此，在 Ca2+ 流出模式下，Na+/Ca2+ 交换器（例如 NCKX3 和 NCX3）可能通过控制 Ca2+ 动员的持续阶段在 Ag 诱导的肥大细胞激活中发挥作用。
Mast cells rely on Ca2+ signaling to initiate activation programs leading to release of proinflammatory mediators. The interplay between Ca2+ release from internal stores and Ca2+ entry through store-operated Ca2+ channels has been extensively studied. Using rat basophilic leukemia (RBL) mast cells and murine bone marrow-derived mast cells, we examine the role of Na+/Ca2+ exchangers. Calcium imaging experiments and patch clamp current recordings revealed both K+-independent and K+-dependent components of Na+/Ca2+ exchange. Northern blot analysis indicated the predominant expression of the K+-dependent sodium-calcium exchanger NCKX3. Transcripts of the exchangers NCX3 and NCKX1 were additionally detected in RBL cells with RT-PCR. The Ca2+ clearance via Na+/Ca2+ exchange represented similar to50% of the total clearance when Ca2+ signals reached levels greater than or equal to200 nM. Ca2+ signaling and store-operated Ca2+ entry were strongly reduced by inverting the direction of Na+/Ca2+ exchange, indicating that Na+/Ca2+ exchangers normally extrude Ca2+ ions from cytosol and prevent the Ca2+-dependent inactivation of store-operated Ca2+ channels. Working in the Ca2+ efflux mode, Na+/Ca2+ exchangers such as NCKX3 and NCX3 might, therefore, play a role in the Ag-induced mast cell activation by controlling the sustained phase of Ca2+ mobilization.