Extracellular pH alkalinization by Cl-/HCO3- exchanger is crucial for TASK2 activation by hypotonic shock in proximal cell lines from mouse kidney
Extracellular pH alkalinization by Cl-/HCO3- exchanger is crucial for TASK2 activation by hypotonic shock in proximal cell lines from mouse kidney
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DOI：
10.1152/ajprenal.00132.2006
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发表时间：
2007-02-01
影响因子：
4.2
通讯作者：
Poujeol, P.
中科院分区：
文献类型：
--
作者：
L'Hoste, S.;Barriere, H.;Poujeol, P.
本研究旨在确定小鼠肾脏近端细胞系RVD期间TASK 2通道激活的机制。为此，采用膜片钳全细胞技术研究了pH值和外浴缓冲能力对低渗休克时Cl-和K+电流的影响。在存在高缓冲液浓度（30 mM HEPES）的情况下，细胞不经历RVD，也不产生外向K+电流（TASK 2）。有趣的是，低渗休克降低了野生型细胞的胞质pH（pH（i））并增加了外部pH（pH（e）），但在cftr（-/-）细胞中没有。DIDS的抑制作用表明，在野生型细胞中由低渗诱导的pH（i）的酸化和pH（e）的碱化可能是由于HCO 3-的排出。这些结果表明，Cl-流入将通过Cl-/HCO 3（-）交换器的活化而成为HCO 3-流出的驱动力。这种HCO 3-的流出然后使pH（e）碱化，这反过来激活TASK 2通道。
The aim of this study was to determine the mechanism responsible for the activation of TASK2 channels during RVD in proximal cell lines from mouse kidney. For this purpose, the patch-clamp whole-cell technique was used to test the effect of pH and the buffering capacity of external bath on Cl- and K+ currents during hypotonic shock. In the presence of a high buffer concentration ( 30 mM HEPES), the cells did not undergo RVD and did not develop outward K+ currents ( TASK2). Interestingly, the hypotonic shock reduced the cytosolic pH (pH(i)) and increased the external pH (pH(e)) in wild-type but not in cftr (-/-) cells. The inhibitory effect of DIDS suggests that the acidification of pH(i) and the alkalinization of pH(e) induced by hypotonicity in wild-type cells could be due to an exit of HCO3-. In conclusion, these results indicate that Cl- influx will be the driving force for HCO3- exit through the activation of the Cl-/HCO3 (-) exchanger. This efflux of HCO3 - then alkalinizes pH(e), which in turn activates TASK2 channels.