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Cyclic AMP Recruits a Discrete Intracellular Ca$^{2+}$ Store by Unmasking Hypersensitive IP$_{3}$ Receptors

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Konieczny, V 
Tovey, SC 
Mataragka, S 
Prole, DL 
Taylor, CW 


Inositol 1,4,5-trisphosphate (IP3) stimulates Ca2+ release from the endoplasmic reticulum (ER), and the response is potentiated by 3',5'-cyclic AMP (cAMP). We investigated this interaction in HEK293 cells using carbachol and parathyroid hormone (PTH) to stimulate formation of IP3 and cAMP, respectively. PTH alone had no effect on the cytosolic Ca2+ concentration, but it potentiated the Ca2+ signals evoked by carbachol. Surprisingly, however, the intracellular Ca2+ stores that respond to carbachol alone could be both emptied and refilled without affecting the subsequent response to PTH. We provide evidence that PTH unmasks high-affinity IP3 receptors within a discrete Ca2+ store. We conclude that Ca2+ stores within the ER that dynamically exchange Ca2+ with the cytosol maintain a functional independence that allows one store to be released by carbachol and another to be released by carbachol with PTH. Compartmentalization of ER Ca2+ stores adds versatility to IP3-evoked Ca2+signals.



cyclic AMP, endoplasmic reticulum, inositol 1,4,5-trisphosphate, intracellular Ca(2+) store, IRBIT, Golgi apparatus, parathyroid hormone, phospholipase C

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Cell Reports

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Biotechnology and Biological Sciences Research Council (BB/L000075/1)
BBSRC (1501541)
Wellcome Trust (101844/Z/13/Z)
This work was supported by the Wellcome Trust (grant 101844) and the Biotechnology and Biological Sciences Research Council (BBSRC) (grant L000075). V.K. was supported by the German Academic Exchange Service. V.K. and S.M. were supported by studentships from the BBSRC. S.C.T. is now an employee of Cairn Research.