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Extracellular ATP Stimulates Exocytosis via Localized Ca 2+ Release from Acidic Stores in Rat Pancreatic β Cells
Author(s) -
Xie Li,
Zhang Ming,
Zhou Wei,
Wu Zhengxing,
Ding Jiuping,
Chen Liangyi,
Xu Tao
Publication year - 2006
Publication title -
traffic
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.677
H-Index - 130
eISSN - 1600-0854
pISSN - 1398-9219
DOI - 10.1111/j.1600-0854.2006.00401.x
Subject(s) - exocytosis , extracellular , thapsigargin , biology , ionomycin , intracellular , microbiology and biotechnology , secretion , bapta , egta , biophysics , biochemistry , medicine , calcium
Three different methods, membrane capacitance ( C m ) measurement, amperometry and FM dye labeling were used to investigate the role of extracellular ATP in insulin secretion from rat pancreatic β cells. We found that extracellular application of ATP mobilized intracellular Ca 2+ stores and synchronously triggered vigorous exocytosis. No influence of ATP on the readily releasable pool of vesicles was observed, which argues against a direct modulation of the secretory machinery at a level downstream of Ca 2+ elevation. The stimulatory effects of ATP were greatly reduced by intracellular perfusion of BAPTA but not EGTA, suggesting a close spatial association of fusion sites with intracellular Ca 2+ releasing sites. ATP‐induced Ca 2+ transients and exocytosis were not blocked by thapsigargin (TG), by a ryanodine receptor antagonist or by dissipation of pH in acidic stores by monensin alone, but they were greatly attenuated by IP 3 receptor inhibition as well as ionomycin plus monensin, suggesting involvement of IP 3 ‐sensitive acidic Ca 2+ stores. Taken together, our data suggest that extracellular ATP triggers exocytosis by mobilizing spatially limited acidic Ca 2+ stores through IP 3 receptors. This mechanism may explain how insulin secretion from the pancreas is coordinated through diffusible ATP that is co‐released with insulin.

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