Regulation of Calcium in Salivary Gland Secretion

Open Access
Publisher Website
Google Scholar
Abstract
Neurotransmitter-regulation of fluid secretion in the salivary glands is achieved by a coordinated sequence of intracellular signaling events, including the activation of membrane receptors, generation of the intracellular second messenger, inositol 1,4,5, trisphosphate, internal Ca2+release, and Ca2+influx. The resulting increase in cytosolic [Ca2+] ([Ca2+]i) regulates a number of ion transporters, e.g., Ca2+-activated K+ channel, Na+/K+/2Cl-co-transporter in the basolateral membrane, and the Ca2+-activated Cl-channel in the luminal membrane, which are intricately involved in fluid secretion. Thus, regulation of [Ca2+]iis central to the regulation of salivary acinar cell function and is achieved by the concerted activities of several ion channels and Ca2+-pumps localized in various cellular membranes. Ca2+ pumps, present in the endoplasmic reticulum and the plasma membrane, serve to remove Ca2+from the cytosol. Ca2+ channels present in the endoplasmic reticulum and the plasma membrane facilitate rapid influx of Ca2+into the cytosol from the internal Ca2+stores and from the external medium, respectively. It is well-established that prolonged fluid secretion is regulated via a sustained elevation in [Ca2+]ithat is primarily achieved by the influx of Ca2+into the cell from the external medium. This Ca2+influx occurs via a putative plasma-membrane-store-operated Ca2+channel which has not yet been identified in any non-excitable cell type. Understanding the molecular nature of this Ca2+ influx mechanism is critical to our understanding of Ca2+signaling in salivary gland cells. This review focuses on the various active and passive Ca2+transport mechanisms in salivary gland cells-their localization, regulation, and role in neurotransmitter-regulation of fluid secretion. In addition to a historical perspective of Ca2+signaling, recent findings and challenging problems facing this field are highlighted.