Deletion of Slc26a6 alters the stoichiometry of apical Cl-/HCO3- exchange in mouse pancreatic duct
Deletion of Slc26a6 alters the stoichiometry of apical Cl-/HCO3- exchange in mouse pancreatic duct
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DOI：
10.1152/ajpcell.00151.2012
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发表时间：
2012-10-01
影响因子：
5.5
通讯作者：
Ishiguro, Hiroshi
中科院分区：
文献类型：
--
作者：
Song, Ying;Yamamoto, Akiko;Ishiguro, Hiroshi
Song Y，Yamamoto A，Steward MC，Ko SB，Stewart AK，Soleimani M，Liu BC，Kondo T，Jin CX，Ishiguro H. Slc 26 a6的缺失改变了小鼠胰管顶端Cl-/HCO 3-交换的化学计量。美国生理学杂志细胞生理学303：C815-C824，2012年。首次发表于2012年8月15日; doi：10.1152/ajpcell.00151.2012。为了确定胰管细胞顶端膜中Cl-/HCO 3-交换器的化学计量和分子特性，同时测量了从野生型和Slc 26 a6缺失小鼠分离的小叶间胰管中的管腔pH和体积的变化。在阴离子梯度的存在下，有利于细胞内HCO 3-与腔Cl-在cAMP刺激的导管快速交换的HCO 3-和Cl-的跨上皮通量进行测量。Cl-吸收/HCO 3-分泌的通量比在野生型导管中类似于0.7，在Slc 26 a6（-/-）导管中类似于1.4，其中发现不同的Cl-/HCO 3-交换器，最可能是SLC 26 A3，是活性的。在cAMP刺激的导管中，Cl-/HCO 3-交换和囊性纤维化跨膜传导调节因子（CFTR）之间的相互作用通过测量乙酸盐预脉冲碱负荷后细胞内pH的恢复来检查。CFTRinh-172的腔内应用诱导的超极化增强了野生型导管中通过SLC 26 A6穿过顶膜的HCO 3流出，但显著降低了Slc 26 a6（-/-）导管中的HCO 3流出。在微灌注的野生型导管中，去除管腔Cl-或管腔应用二氢-4，4 '-二异硫氰基芪-2，2'-二磺酸来抑制SLC 26 A6，引起膜超极化，这在SLC 26 a6（-/-）导管中被消除。总之，我们已经证明，删除Slc 26 a6改变了表观化学计量的顶端Cl-/HCO 3-交换在本地胰管。我们的结果与SLC 26 A6介导1：2 Cl-/HCO 3-交换一致，并且交换器在其不存在时上调，最可能是SLC 26 A3，介导2：1交换。
Song Y, Yamamoto A, Steward MC, Ko SB, Stewart AK, Soleimani M, Liu BC, Kondo T, Jin CX, Ishiguro H. Deletion of Slc26a6 alters the stoichiometry of apical Cl-/HCO3- exchange in mouse pancreatic duct. Am J Physiol Cell Physiol 303: C815-C824, 2012. First published August 15, 2012; doi:10.1152/ajpcell.00151.2012.-To define the stoichiometry and molecular identity of the Cl-/HCO3- exchanger in the apical membrane of pancreatic duct cells, changes in luminal pH and volume were measured simultaneously in interlobular pancreatic ducts isolated from wild-type and Slc26a6-null mice. Transepithelial fluxes of HCO3- and Cl- were measured in the presence of anion gradients favoring rapid exchange of intracellular HCO3- with luminal Cl- in cAMP-stimulated ducts. The flux ratio of Cl- absorption/HCO3- secretion was similar to 0.7 in wild-type ducts and similar to 1.4 in Slc26a6(-/-) ducts where a different Cl-/HCO3- exchanger, most likely SLC26A3, was found to be active. Interactions between Cl-/HCO3- exchange and cystic fibrosis transmembrane conductance regulator (CFTR) in cAMP-stimulated ducts were examined by measuring the recovery of intracellular pH after alkali-loading by acetate prepulse. Hyperpolarization induced by luminal application of CFTRinh-172 enhanced HCO3- efflux across the apical membrane via SLC26A6 in wild-type ducts but significantly reduced HCO3- efflux in Slc26a6(-/-) ducts. In microperfused wild-type ducts, removal of luminal Cl-, or luminal application of dihydro-4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid to inhibit SLC26A6, caused membrane hyperpolarization, which was abolished in Slc26a6(-/-) ducts. In conclusion, we have demonstrated that deletion of Slc26a6 alters the apparent stoichiometry of apical Cl-/HCO3- exchange in native pancreatic duct. Our results are consistent with SLC26A6 mediating 1:2 Cl-/HCO3- exchange, and the exchanger upregulated in its absence, most probably SLC26A3, mediating 2:1 exchange.