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TRPM7 Is Involved in Volume Regulation in Salivary Glands #MMPMID28499095
Kim JM; Choi S; Park K
J Dent Res 2017[Aug]; 96 (9): 1044-1050 PMID28499095show ga
Under hypotonic conditions, the regulatory volume decrease (RVD) is essential to maintain physiological homeostasis and functions in diverse biological systems. Intracellular Ca(2+) has been reported as an important mediator of this response, but the underlying Ca(2+) mechanism responsible for RVD is still controversial. Here we investigate the role of Ca(2+) 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 Ca(2+) chelation completely inhibited the RVD response. The incidence and magnitude of the Ca(2+) transient were proportional to the degree of hypotonicity of the extracellular medium, and there was a close relationship between intracellular Ca(2+) concentration and the volumetric changes of the cells. Notably, this response was mediated by Ca(2+)-induced Ca(2+) release, which is triggered by Ca(2+) 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 Ca(2+)-activated Cl(-) currents. A specific inhibitor of Cl(-) currents also inhibited the RVD response. In conclusion, an intracellular Ca(2+) increase in response to osmotically induced cell swelling plays a critical role in RVD in salivary gland acinar cells.