Secretion and cell volume regulation by salivary acinar cells from mice lacking expression of the Clcn3 Cl- channel gene
Secretion and cell volume regulation by salivary acinar cells from mice lacking expression of the Clcn3 Cl- channel gene
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DOI：
10.1113/jphysiol.2002.021980
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发表时间：
2002-11-15
影响因子：
5.5
通讯作者：
Melvin, JE
中科院分区：
文献类型：
--
作者：
Arreola, J;Begenisich, T;Melvin, JE
唾液腺腺泡细胞收缩时，Cl-电流激活细胞肿胀诱导暴露于低渗溶液或响应钙动员激动剂。尽管ClC-3在几种组织中作为细胞体积敏感性Cl-通道，但参与这些过程的唾液细胞中Cl-通道的分子特性尚不清楚。我们发现，从Clcn 3基因靶向破坏的小鼠中分离的细胞以类似于野生型同窝仔细胞的方式进行调节体积减少。与正常的调节性体积减少反应一致，来自ClC-3缺陷小鼠的细胞中溶胀激活的Cl-电流的幅度和动力学与来自野生型小鼠的那些相当。也有人认为ClC-3是由Ca 2 +-钙调蛋白依赖性蛋白激酶II激活的;然而，在Clcn 3（-/-）动物中，Ca 2 +-依赖性Cl-电流的幅度没有变化。此外，我们观察到ClC-3似乎在腺血管的平滑肌细胞中高度表达，这表明该通道通过调节血流在唾液产生中的潜在作用，但野生型和无效突变动物体内刺激唾液的体积和离子组成是相当的。最后，在一些细胞中，ClC-3是一种细胞内通道，被认为参与囊泡酸化和分泌。然而，唾液中的蛋白质含量在Clcn 3（-/-）小鼠中没有变化。我们的研究结果表明，ClC-3氯离子通道是不是一个主要的调节腺泡细胞的体积，也不是必不可少的确定分泌速率和组成的唾液。
Salivary gland acinar cells shrink when Cl- currents are activated following cell swelling induced by exposure to a hypotonic solution or in response to calcium-mobilizing agonists. The molecular identity of the Cl- channel(s) in salivary cells involved in these processes is unknown, although ClC-3 has been implicated in several tissues as a cell-volume-sensitive Cl- channel. We found that cells isolated from mice with targeted disruption of the Clcn3 gene undergo regulatory volume decrease in a fashion similar to cells from wild-type littermates. Consistent with a normal regulatory volume decrease response, the magnitude and the kinetics of the swell-activated Cl- currents in cells from ClC-3-deficient mice were equivalent to those from wild-type mice. It has also been suggested that ClC-3 is activated by Ca2+-calmodulin-dependent protein kinase II; however, the magnitude of the Ca2+-dependent Cl- current was unchanged in the Clcn3(-/-) animals. In addition, we observed that ClC-3 appeared to be highly expressed in the smooth muscle cells of glandular blood vessels, suggesting a potential role for this channel in saliva production by regulating blood flow, yet the volume and ionic compositions of in vivo stimulated saliva from wild-type and null mutant animals were comparable. Finally, in some cells ClC-3 is an intracellular channel that is thought to be involved in vesicular acidification and secretion. Nevertheless, the protein content of saliva was unchanged in Clcn3(-/-) mice. Our results demonstrate that the ClC-3 Cl- channel is not a major regulator of acinar cell volume, nor is it essential for determining the secretion rate and composition of saliva.