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肝癌细胞中张力激活型和体积激活型 Cl⁻ 电流之间缺乏关联。

Lack of association between stretch-activated and volume-activated Cl⁻ currents in hepatocellular carcinoma cells.

机构信息

Guangdong Key Laboratory for Bioactive Drugs Research and Department of Biology, Guangdong Pharmaceutical University, Guangzhou, China.

出版信息

J Cell Physiol. 2011 May;226(5):1176-85. doi: 10.1002/jcp.22443.

DOI:10.1002/jcp.22443
PMID:20945353
Abstract

Stretch-activated chloride currents (I(Cl,SA) ) have been considered to be a component of volume-activated chloride currents (I(Cl,vol) ) for some time. This is due to a similarity in biophysical and pharmacological properties that involve a membrane curvature-induced mechanism and rearrangement of the cytoskeleton induced by cell swelling or membrane stretch. In the present study, we demonstrated that current density, along with the time taken from the activation of currents to the peak, were significantly different between the two currents, in highly metastatic human hepatocellular carcinoma cells. In addition, the activation of I(Cl,vol) or I(Cl,SA), induced maximally by hypotonic solutions or membrane stretch, respectively, did not affect the following activation of the other one. Moreover, neither inhibition of I(Cl,vol) by sh-ClC-3 transfection, nor functional blocking of I(Cl,vol) by intracellular dialysis of anti-ClC-3 antibody had an effect on the activation and properties of I(Cl,SA). Collectively, our results suggest that I(Cl,SA) is different from I(Cl,vol) in activation mechanism and/or in molecular entity responsible for formation of the currents. ClC-3 is involved in the activation of I(Cl,vol), but not of I(Cl,SA).

摘要

伸展激活氯离子电流(I(Cl,SA))在一段时间以来一直被认为是体积激活氯离子电流(I(Cl,vol))的一个组成部分。这是由于涉及膜曲率诱导机制和细胞肿胀或膜拉伸诱导的细胞骨架重排的生物物理和药理学特性的相似性。在本研究中,我们证明在高转移性人肝癌细胞中,两种电流的电流密度以及从电流激活到峰值所需的时间之间存在显著差异。此外,由低渗溶液或膜拉伸分别最大程度激活的 I(Cl,vol)或 I(Cl,SA)的激活不会影响另一个电流的后续激活。此外,sh-ClC-3 转染抑制 I(Cl,vol)或内源性透析抗 ClC-3 抗体阻断 I(Cl,vol)的功能均对 I(Cl,SA)的激活和特性没有影响。总的来说,我们的结果表明 I(Cl,SA)在激活机制和/或负责形成电流的分子实体方面与 I(Cl,vol)不同。ClC-3 参与 I(Cl,vol)的激活,但不参与 I(Cl,SA)的激活。

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