Mechanism of Calcium Waves and Oscillations in Non-Excitable Cells
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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 Ca2+ ([Ca2+]i) and cyclic AMP (cAMP) production. Ca2+ plays essential roles in fluid and electrolyte secretions from salivary acinar cells. A typical agonist-induced Ca2+ response in salivary acinar cells shows Ca2+ waves, in which the rise in [Ca2+]i is initiated at the apical pole before spreading towards the basal region of the cell. Ca2+ responses with low concentrations of agonist often occur result in repetitive transient rises in [Ca2+]i, which have been referred to as Ca2+ oscillations. These spatial characteristics of the Ca2+ signal are primarily determined by the distribution of the endoplasmic reticulum (ER) and inositol 1,4,5-trisphosphate (IP3) receptors, which correspond to the major intracellular Ca2+ store and Ca2+ 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 Ca2+-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 Ca2+ store, accumulating evidence indicates that mitochondria play a significant role in the regulation of the spatial and temporal patterns of Ca2+ signals. The mechanism that is responsible for Ca2+ oscillations remain controversial. Two general models for Ca2+ oscillations have been proposed ; one explains Ca2+ oscillations generated by constant cytoplasmic IP3 concentrations [IP3]i) and the other explains Ca2+ oscillations generated by oscillating [IP3]i. Quantitative measurements of [IP3]i using fluorescent IP3 biosensors revealed two cell type-specific differences in IP3 dynamics : non-fluctuating rises in [IP3]i and repetitive IP3 spikes during Ca2+ oscillations. However, the repetitive IP3 spikes are thought to be passive reflections of Ca2+ oscillations, and are unlikely to be essential for driving Ca2+ oscillations. Regarding the mechanism of Ca2+ oscillations, the importance of dual feedback effects of Ca2+ on IP3Rs 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 Ca2+ oscillations, an important challenge for the future will be to determine how these patterns of Ca2+ signaling systems function in specific cellular processes.
- 日本大学松戸歯学部 口腔科学研究所の論文
日本大学松戸歯学部 口腔科学研究所 | 論文
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