Ca2+ signaling and regulation of fluid secretion in salivary gland acinar cells

Neurotransmitter stimulation of plasma membrane receptors stimulates salivary gland fluid secretion via a complex process that is determined by coordinated temporal and spatial regulation of several Ca2+ signaling processes as well as ion flux systems. Studies over the past four decades have demonstrated that Ca2+ is a critical factor in the control of salivary gland function. Importantly, critical components of this process have now been identified, including plasma membrane receptors, calcium channels, and regulatory proteins. The key event in activation of fluid secretion is an increase in intracellular [Ca2+] ([Ca2+](i)) triggered by IP3-induced release of Ca2+ from ER via the IP3R. This increase regulates the ion fluxes required to drive vectorial fluid secretion. IP3R. This determine the site of initiation and the pattern of [Ca2+](i) signal in the cell. However, Ca2+ entry into the cell is required to sustain the elevation of [Ca2+](i); and fluid secretion. This Ca2+ influx pathway, store-operated calcium influx pathway (SOCE), has been studied in great detail and the regulatory mechanisms as well as key molecular components have now been identified. Orai1, TRPC1, and STIM1 are critical components of SOCE and among these, Ca2+ entry via TRPC1 is a major determinant of fluid secretion. The receptor-evoked Ca2+ signal in salivary gland acinar cells is unique in that it starts at the apical pole and then rapidly increases across the cell. The basis for the polarized Ca2+ signal can be ascribed to the polarized arrangement of the Ca2+ channels, transporters, and signaling proteins. Distinct localization of these proteins in the cell suggests compartmentalization of Ca2+ signals during regulation of fluid secretion. This chapter will discuss new concepts and findings regarding the polarization and control of Ca2+ signals in the regulation of fluid secretion. Published by Elsevier Ltd.