Secretagogue stimulated intracellular Ca2+ signals are fundamentally important for initiating the secretion of the fluid and ion component of saliva from parotid acinar cells. The Ca2+ signals have characteristic spatial and temporal characteristics which are defined by the specific properties of Ca2+ release mediated by inositol 1,4,5-trisphosphate receptors (InsP3R). In this study we have investigated the role of adenine nucleotides in modulating Ca2+ release in mouse parotid acinar cells. In permeabilized cells, the Ca2+ release rate induced by submaximal [InsP3] was increased by 5 mM ATP. Enhanced Ca2+ release was not observed at saturating [InsP3]. The EC50 for the augmented Ca2+ release was ~8 μM ATP. The effect was mimicked by non-hydrolysable ATP analogs. ADP and AMP also potentiated Ca2+ release but were less potent than ATP. In acini isolated from InsP3R-2 null transgenic animals the rate of Ca2+ release was decreased under all conditions but now enhanced by ATP at all [InsP3]. In addition the EC50 for ATP potentiation increased to ~500 μM. These characteristics are consistent with the properties of the InsP3R-2 dominating the overall features of InsP3R-induced Ca2+ release despite the expression of all isoforms. Finally, Ca2+ signals were measured in intact parotid lobules by multi-photon microscopy. Consistent with the release data, CCh-stimulated Ca2+ signals were reduced in lobules exposed to experimental hypoxia when compared to control lobules only at sub-maximal concentrations. Adenine nucleotide modulation of InsP3R in parotid acinar cells likely contributes to the properties of Ca2+ signals in physiological and pathological conditions.
- inositol 1,4,5-trisphosphate receptors
- parotid acinar cells
- Ca2+ release
- Copyright © 2011, American Journal of Physiology- Gastrointestinal and Liver Physiology