Regulation of calcium in salivary gland secretion.
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+]i is 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+]i that 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.
Ambudkar
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Secretory Physiology Section, Gene Therapy and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA.
D000818:Animals; D002118:Calcium / Q000502:physiology*; D015220:Calcium Channels / Q000502:physiology; D020013:Calcium Signaling / Q000502:physiology; D002135:Calcium-Binding Proteins / Q000502:physiology; D000252:Calcium-Transporting ATPases / Q000502:physiology; D002462:Cell Membrane / Q000502:physiology; D006801:Humans; D012469:Salivary Glands / Q000378:metabolism*; D012472:Salivation / Q000502:physiology*
D015220:Calcium Channels; D002135:Calcium-Binding Proteins; D000252:Calcium-Transporting ATPases; D002118:Calcium