TRPM7 Is Involved in Volume Regulation in Salivary Glands
TRPM7 Is Involved in Volume Regulation in Salivary Glands
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DOI：
10.1177/0022034517708766
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发表时间：
2017-08-01
影响因子：
7.6
通讯作者：
Park, K.
中科院分区：
文献类型：
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作者：
Kim, J. M.;Choi, S.;Park, K.
在低渗条件下，调节性容积减少（RVD）对于维持各种生物系统的生理稳态和功能至关重要。细胞内Ca ~（2+）已被报道为这种反应的重要介质，但负责RVD的潜在Ca ~（2+）机制仍有争议。在这里，我们调查的作用，钙离子在RVD反应使用活细胞成像，显微荧光光谱法，和膜片钳技术。一个典型的RVD观察下颌下腺腺泡细胞肿胀后，在低渗溶液中，而细胞内钙离子螯合完全抑制RVD反应。Ca 2+瞬变的发生率和幅度与细胞外介质的低渗程度成正比，并且细胞内Ca 2+浓度与细胞体积变化之间存在密切关系。值得注意的是，这种反应是由Ca 2+诱导的Ca 2+释放介导的，这是由经由牵张激活的TRPM 7通道的Ca 2+内流触发的。此外，我们检测到在肿胀的腺泡细胞在低渗应力时产生的Cl-电流，和电流的配置文件相匹配的Ca 2+激活的Cl-电流。Cl-电流的特异性抑制剂也抑制RVD反应。总之，细胞内Ca 2+的增加，响应于炎症诱导的细胞肿胀在唾液腺泡细胞的RVD中起着关键作用。
Under hypotonic conditions, the regulatory volume decrease (RVD) is essential to maintain physiological homeostasis and functions in diverse biological systems. Intracellular Ca2+ has been reported as an important mediator of this response, but the underlying Ca2+ mechanism responsible for RVD is still controversial. Here we investigate the role of Ca2+ in the RVD response using live-cell imaging, microspectrofluorimetry, and a patch-clamp technique. A typical RVD was observed in submandibular gland acinar cells after swelling in a hypotonic solution, whereas intracellular Ca2+ chelation completely inhibited the RVD response. The incidence and magnitude of the Ca2+ transient were proportional to the degree of hypotonicity of the extracellular medium, and there was a close relationship between intracellular Ca2+ concentration and the volumetric changes of the cells. Notably, this response was mediated by Ca2+-induced Ca2+ release, which is triggered by Ca2+ influx via stretch-activated TRPM7 channels. Furthermore, we detected the generation of Cl- currents in the swelling acinar cells upon hypotonic stress, and the current profile matched that of the Ca2+-activated Cl- currents. A specific inhibitor of Cl- currents also inhibited the RVD response. In conclusion, an intracellular Ca2+ increase in response to osmotically induced cell swelling plays a critical role in RVD in salivary gland acinar cells.