Cyclic AMP Recruits a Discrete Intracellular Ca2+ Store by Unmasking Hypersensitive IP3 Receptors

Publication date: 17 January 2017
Source:Cell Reports, Volume 18, Issue 3
Author(s): Vera Konieczny, Stephen C. Tovey, Stefania Mataragka, David L. Prole, Colin W. Taylor
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.

Graphical abstract

Teaser

Cyclic AMP directly potentiates IP3-evoked Ca²⁺ release. Konieczny et al. find that IP3 alone and IP3 with cAMP release Ca²⁺ from independent stores within the endoplasmic reticulum. Compartmentalized Ca²⁺ stores increase the versatility of IP3-mediated Ca²⁺ signaling.


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