TRPM7 Is Involved in Volume Regulation in Salivary Glands

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.