Characterization of SLC26A9, facilitation of Cl- transport by bicarbonate
Characterization of SLC26A9, facilitation of Cl- transport by bicarbonate
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DOI：
10.1159/000149780
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发表时间：
2008-01-01
影响因子：
--
通讯作者：
Ehrenfeld, Jordi
中科院分区：
文献类型：
--
作者：
Loriol, Celine;Dulong, Sandrine;Ehrenfeld, Jordi
SLC 26家族成员是阴离子转运蛋白，参与上皮细胞Cl-和HCO 3-的吸收或分泌。SLC 26 A9优先在肺中表达，是该家族中特征较差的成员。在这项研究中，我们研究了人SLC 26 A9的转运特性，以确定其功能和药理学特性。SLC 26 A9蛋白表达导致阴离子电流的出现，表现出明显的线性电流/电压关系，并增加Cl-36流入和流出。结果表明，电导率为Cl- > I- > NO3- >葡萄糖酸盐> SO 42-，选择性（P-x/P-Cl）为I- > NO3- > Cl- >葡萄糖酸盐> SO 42-，Cl-通道抑制剂DIDS和NS 3623可抑制SLC 26 A9的电流，而CFTR（inh）-172或格列本脲则无明显抑制作用。细胞内cAMP（一种CFTR激活剂）的升高也是无效的，而增加细胞内钙离子阻断了SLC 26 A9相关的电流。由SLC 26 A9蛋白表达介导的HCO 3-电导率低，并且在有利于Cl-/HCO 3-交换的条件下检测不到细胞内pHi变化。然而，HCO 3-/CO2的存在下刺激的Cl-转运活性的SLC 26 A9在非洲爪蟾卵母细胞或SLC 26 A9转导的COS-7细胞。作为表征SLC 26 A9功能的重要的初始步骤，我们得出结论，SLC 26 A9是一个Cl-通道，我们建议HCO 3-作为通道的调制器。SLC 26 A9在气道上皮中的生理作用及其与CFTR的潜在相互作用仍有待阐明。版权所有（C）2008 S. Karger AG，巴塞尔。
SLC26 family members are anionic transporters involved in Cl-and HCO3- absorption or secretion in epithelia. SLC26A9, preferentially expressed in the lung, is a poorly characterized member of this family. In this study, we investigated the transport properties of human SLC26A9 to determine its functional and pharmacological characteristics. SLC26A9 protein expression results in the appearance of an anionic current exhibiting an apparently linear current/voltage relationship and increases in Cl-36 influxes and effluxes. The sequences of conductivity, Cl- > I- > NO3- >= gluconate > SO42- and selectivity (P-x/P-Cl), I- > NO3- > Cl- > gluconate > SO42- are found. Cl- channel inhibitors DIDS and NS 3623 inhibit SLC26A9 associated currents while the specific CFTR inhibitor (CFTR(inh)-172) or glybenclamide has little effect. Elevation of intracellular cAMP (a CFTR activator) is also ineffective whereas increasing intracellular calcium blocks the SLC26A9 associated currents.The HCO3- conductance mediated by the SLC26A9 protein expression is low and no intracellular pHi changes are detectable under conditions favoring a Cl-/HCO3- exchange. However, the presence of HCO3-/CO2 stimulates the Cl--transporting activity of SLC26A9 in Xenopus laevis oocytes or SLC26A9-transduced COS-7 cells. As an important initial step in characterizing SLC26A9 function, we conclude that SLC26A9 is a Cl- channel and we suggest that HCO3- acts as a modulator of the channel. SLC26A9 physiological role in airway epithelia and its potential interaction with CFTR remain to be elucidated. Copyright (C) 2008 S. Karger AG, Basel.