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Extracellular ATP stimulates exocytosis via localized Ca(2+) release from acidic stores in rat pancreatic beta cells.
- Source :
-
Traffic (Copenhagen, Denmark) [Traffic] 2006 Apr; Vol. 7 (4), pp. 429-39. - Publication Year :
- 2006
-
Abstract
- 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 beta 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.
- Subjects :
- Animals
Caffeine metabolism
Calcium Channels metabolism
Cells, Cultured
Dantrolene metabolism
Electrophysiology
Enzyme Inhibitors metabolism
Fluorescent Dyes metabolism
Inositol 1,4,5-Trisphosphate Receptors
Insulin-Secreting Cells cytology
Male
Muscle Relaxants, Central metabolism
Pyridinium Compounds metabolism
Quaternary Ammonium Compounds metabolism
Rats
Rats, Wistar
Receptors, Cytoplasmic and Nuclear metabolism
Receptors, Purinergic P2 metabolism
Ryanodine Receptor Calcium Release Channel metabolism
Thapsigargin metabolism
Adenosine Triphosphate metabolism
Calcium metabolism
Exocytosis physiology
Hydrogen-Ion Concentration
Insulin metabolism
Insulin-Secreting Cells metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1398-9219
- Volume :
- 7
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Traffic (Copenhagen, Denmark)
- Publication Type :
- Academic Journal
- Accession number :
- 16536741
- Full Text :
- https://doi.org/10.1111/j.1600-0854.2006.00401.x