Clcn2 encodes the hyperpolarization-activated chloride channel in the ducts of mouse salivary glands.
Clcn2 encodes the hyperpolarization-activated chloride channel in the ducts of mouse salivary glands.
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Clcn2 编码小鼠唾液腺导管中的超极化激活的氯离子通道。
DOI：
10.1152/ajpgi.90384.2008
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Melvin,JamesE
中科院分区：
文献类型：
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作者：
Romanenko,VictorG;Nakamoto,Tetsuji;Catalán,MarceloA;Gonzalez-Begne,Mireya;Schwartz,GeorgeJ;Jaramillo,Yasna;Sepúlveda,FranciscoV;Figueroa,CarlosD;Melvin,JamesE
在唾液腺导管中跨上皮氯−转运是离子重吸收过程的主要组成部分，离子重吸收过程是唾液产生的最后阶段。先前的研究表明，具有ClC-2通道生物物理特性的Cl-−电流控制着小鼠颌下腺未受刺激的颗粒导管细胞的Cl-−电导。这种内向整流的Cl-−电流被超极化和细胞内Cl-−浓度升高所激活。在这里，我们发现ClC-2免疫定位于小鼠唾液腺的腺泡和导管细胞的基底外侧区域，而它在颗粒和纹状导管细胞中的表达最强。与此观察一致的是，颗粒导管细胞的ClC-2样电流比颌下腺的腺泡细胞大近10倍。Clcn2−小鼠细胞内向整流性ClC−/−电流的丧失证实了导致这些电流的通道的分子同一性为ClC-2。然而，体内和体外液体分泌分析都没有发现Clcn2−/−小鼠离子成分、渗透压或唾液流速的显著变化。此外，在Clcn2基因缺失的小鼠中，既没有检测到CFTRCI−通道蛋白表达的代偿性增加，也没有检测到CFTR样CL−电流的代偿性增加，也没有发现ClC-2对血器官屏障功能有重要作用。结论：ClC-2是导管细胞内向整流性的Cl-−通道，但其表达对涎腺导管上皮细胞的离子重吸收或屏障功能并不明显。
Transepithelial Cl−transport in salivary gland ducts is a major component of the ion reabsorption process, the final stage of saliva production. It was previously demonstrated that a Cl−current with the biophysical properties of ClC-2 channels dominates the Cl−conductance of unstimulated granular duct cells in the mouse submandibular gland. This inward-rectifying Cl−current is activated by hyperpolarization and elevated intracellular Cl−concentration. Here we show that ClC-2 immunolocalized to the basolateral region of acinar and duct cells in mouse salivary glands, whereas its expression was most robust in granular and striated duct cells. Consistent with this observation, nearly 10-fold larger ClC-2-like currents were observed in granular duct cells than the acinar cells obtained from submandibular glands. The loss of inward-rectifying Cl−current in cells fromClcn2−/−mice confirmed the molecular identity of the channel responsible for these currents as ClC-2. Nevertheless, both in vivo and ex vivo fluid secretion assays failed to identify significant changes in the ion composition, osmolality, or salivary flow rate ofClcn2−/−mice. Additionally, neither a compensatory increase in Cftr Cl−channel protein expression nor in Cftr-like Cl−currents were detected inClcn2null mice, nor did it appear that ClC-2 was important for blood-organ barrier function. We conclude that ClC-2 is the inward-rectifying Cl−channel in duct cells, but its expression is not apparently required for the ion reabsorption or the barrier function of salivary ductal epithelium.