Volume-Sensitive Chloride Channels are Involved in Maintenance of Basal Cell Volume in Human Acute Lymphoblastic Leukemia Cells
Volume-Sensitive Chloride Channels are Involved in Maintenance of Basal Cell Volume in Human Acute Lymphoblastic Leukemia Cells
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体积敏感氯离子通道参与人急性淋巴细胞白血病细胞基底细胞体积的维持
DOI：
10.1007/s00232-011-9349-7
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发表时间：
2011-03-01
影响因子：
2.4
通讯作者：
Chen, Lixin
中科院分区：
文献类型：
--
作者：
Cao, Guozhen;Zuo, Wanhong;Chen, Lixin
氯通道在不同的细胞中广泛表达。然而，容量激活的氯通道在正常等渗条件下的激活和作用尚不清楚，特别是在淋巴细胞中。本文研究了等渗条件下人急性淋巴细胞白血病Molt4细胞基础氯电流和容量激活氯电流的激活及其在维持基础细胞体积中的作用。采用膜片钳技术和时移图像分析技术记录全细胞电流和细胞体积变化。在等渗条件下，记录到基础氯电流。电流呈弱外向整流，对体积敏感，在观察期内未见明显失活。47%高渗浴溶液和氯离子通道阻滞剂NPPB和他莫昔芬抑制该电流。将细胞暴露在47%低渗浴溶液中，可进一步激活基础电流。低张激活电流具有与基础电流相似的特性，可被NPPB、三苯氧胺、三磷酸腺苷和高渗浴液抑制。此外，细胞外低张刺激使细胞肿胀，并导致调节性体积减少(RVD)。细胞外应用NPPB、三苯氧胺和三磷酸腺苷可在等渗条件下使细胞肿胀，并抑制低张细胞肿胀引起的RVD。这些结果表明，在等渗条件下，一些体积激活的氯通道被激活，导致基础氯电流的出现，这在维持淋巴细胞白血病细胞的基础细胞体积中起着重要作用。当细胞肿胀时，氯离子通道可以被进一步激活以诱导调节性容量恢复。
Chloride channels are expressed ubiquitously in different cells. However, the activation and roles of volume-activated chloride channels under normal isotonic conditions are not clarified, especially in lymphatic cells. In this study, the activation of basal and volume-activated chloride currents and their roles in maintenance of basal cell volume under isotonic conditions were investigated in human acute lymphoblastic leukemia Molt4 cells. The patch-clamp technique and time-lapse image analysis were employed to record whole-cell currents and cell volume changes. Under isotonic conditions, a basal chloride current was recorded. The current was weakly outward-rectified and volume-sensitive and was not inactivated obviously in the observation period. A 47% hypertonic bath solution and the chloride channel blockers NPPB and tamoxifen suppressed the current. Exposure of cells to 47% hypotonic bath solution activated further the basal current. The hypotonicity-activated current possessed properties similar to those of the basal current and was inhibited by NPPB, tamoxifen, ATP and hypertonic bath solution. Furthermore, extracellular hypotonic challenges swelled the cells and induced a regulatory volume decrease (RVD). Extracellular applications of NPPB, tamoxifen and ATP swelled the cells under isotonic conditions and inhibited the RVD induced by hypotonic cell swelling. The results suggest that some volume-activated chloride channels are activated under isotonic conditions, resulting in the appearance of the basal chloride current, which plays an important role in the maintenance of basal cell volume in lymphoblastic leukemia cells. Chloride channels can be activated further to induce a regulatory volume recovery when cells are swollen.