科研之友
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摘要
There is emerging consensus that P2X(4) and P2X(7) ionotropic purinoceptors (P(2)X(4)Rand P2X7R) are critical players in regulating [Ca2+](i) dynamics and fluid secretion in the salivary gland. In contrast, details regarding their compartmentalization and selective activation, contributions to the spatiotemporal properties of intracellular signals and roles in regulating protein exocytosis and ion channel activity have remained largely undefined. To address these concerns, we profiled mouse parotid acinar cells using live-cell imaging to follow the spatial and temporal features of ATP-evoked Ca2+ dynamics and exocytotic activity. Selective activation of P2X(7)Rs revealed an apical-to-basal [Ca2+] i signal that initiated at the sub-luminal border and propagated with a wave speed estimated at 17.3 +/- 4.3 mu ms-1 ( n = 6). The evoked Ca2+ spike consisted of Ca2+ influx and Ca2+-induced Ca2+ release from intracellular Ca2+ channels. In contrast, selective activation of P2X4Rs induced a Ca2+ signal that initiated basally and propagated toward the lumen with a wave speed of 4.3 +/- 0.2 mu ms-1 ( n = 8) that was largely independent of intracellular Ca2+ channel blockade. Consistent with these observations, P2X7R expression was enriched in the sub-luminal regions of acinar cells while P2X4R appeared localized to basal areas. In addition, we showed that P2X4R andP2X7R activation evokes exocytosis in parotid acinar cells. Our studies also demonstrate that the P2X4R-mediated [Ca2+] i rise and subsequent protein exocytosis was enhanced by ivermectin ( IVR). Thus, in addition to furthering our understanding of salivary gland physiology, this study identifies P2X4R as a potential target for treatment of salivary hypofunction diseases.
- 出版日期2012-6
