The functions of salivary acinar cells are regulated by the activation of receptors on their basolateral membranes and by subsequent intracellular signaling events, including increases in cytoplasmic Ca
2+ ([Ca
2+]
i) and cyclic AMP (cAMP) production. Ca
2+ plays essential roles in fluid and electrolyte secretions from salivary acinar cells. A typical agonist-induced Ca
2+ response in salivary acinar cells shows Ca
2+ waves, in which the rise in [Ca
2+]
i is initiated at the apical pole before spreading towards the basal region of the cell. Ca
2+ responses with low concentrations of agonist often occur result in repetitive transient rises in [Ca
2+]
i, which have been referred to as Ca
2+ oscillations. These spatial characteristics of the Ca
2+ signal are primarily determined by the distribution of the endoplasmic reticulum (ER) and inositol 1,4,5-trisphosphate (IP
3) receptors, which correspond to the major intracellular Ca
2+ store and Ca
2+ releasing channels, respectively. ER cisternae are densely packed in the entire basolateral region, whereas small ER vesicular structures are located in the apical region of acinar cells. This apparent paradox would be resolved if it could be shown that the small Ca
2+-releasing ER elements in the apical region are connected to the main part of the ER in the basolateral area. Although the mitochondria are not considered to be a physiological Ca
2+ store, accumulating evidence indicates that mitochondria play a significant role in the regulation of the spatial and temporal patterns of Ca
2+ signals. The mechanism that is responsible for Ca
2+ oscillations remain controversial. Two general models for Ca
2+ oscillations have been proposed ; one explains Ca
2+ oscillations generated by constant cytoplasmic IP
3 concentrations [IP
3]
i) and the other explains Ca
2+ oscillations generated by oscillating [IP
3]
i. Quantitative measurements of [IP
3]
i using fluorescent IP
3 biosensors revealed two cell type-specific differences in IP
3 dynamics : non-fluctuating rises in [IP
3]
i and repetitive IP
3 spikes during Ca
2+ oscillations. However, the repetitive IP
3 spikes are thought to be passive reflections of Ca
2+ oscillations, and are unlikely to be essential for driving Ca
2+ oscillations. Regarding the mechanism of Ca
2+ oscillations, the importance of dual feedback effects of Ca
2+ on IP
3Rs has been demonstrated experimentally, while the precise mechanism responsible for establishing these oscillations remains unclear. In addition to the necessity of continuing work on the mechanisms that control Ca
2+ oscillations, an important challenge for the future will be to determine how these patterns of Ca
2+ signaling systems function in specific cellular processes.
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