Abstract
Mechanisms controlling endoplasmic reticulum (ER) Ca2+ homeostasis are important regulators of resting cytoplasmic Ca2+ concentration ([Ca2+]cyto) and receptor-mediated Ca2+ signalling. Here we investigate channels responsible for ER Ca2+ leak in THP-1 macrophage and human primary macrophage. In the absence of extracellular Ca2+ we employ ionomycin action at the plasma membrane to stimulate ER Ca2+ leak. Under these conditions ionomycin elevates [Ca2+]cyto revealing a Ca2+ leak response which is abolished by thapsigargin. IP3 receptors (Xestospongin C, 2-APB), ryanodine receptors (dantrolene), and translocon (anisomycin) inhibition facilitated ER Ca2+ leak in model macrophage, with translocon inhibition also reducing resting [Ca2+]cyto. In primary macrophage, translocon inhibition blocks Ca2+ leak but does not influence resting [Ca2+]cyto. We identify a role for translocon-mediated ER Ca2+ leak in receptor-mediated Ca2+ signalling in both model and primary human macrophage, whereby the Ca2+ response to ADP (P2Y receptor agonist) is augmented following anisomycin treatment. In conclusion, we demonstrate a role of ER Ca2+ leak via the translocon in controlling resting cytoplasmic Ca2+ in model macrophage and receptor-mediated Ca2+ signalling in model macrophage and primary macrophage.
Original language | English |
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Pages (from-to) | 633–639 |
Number of pages | 7 |
Journal | Biochemical and Biophysical Research Communications |
Volume | 487 |
Issue number | 3 |
Early online date | 20 Apr 2017 |
DOIs | |
Publication status | Published - 3 Jun 2017 |
Keywords
- Endoplasmic reticulum
- Calcium leak
- Translocon
- Macrophage
- Purinergic
Profiles
-
Samuel Fountain
- School of Biological Sciences - Professor of Pharmacology
- Cells and Tissues - Member
Person: Research Group Member, Academic, Teaching & Research