Calcium-induced calcium release mediates all-or-nothing responses of mesenchymal stromal cells to noradrenaline

• Published in: Biochemistry (Moscow). Supplement series A, Membrane and cell biology Membrane and cell biology, 2014, Vol.8 (1), p.82-88
• Main Authors: Kotova, P. D., Turin-Kuzmin, P. A., Rogachevskaja, O. A., Fadeeva, J. I., Sysoeva, V. Yu, Tkachuk, V. A., Kolesnikov, S. S.
• Format: Article
• Language: English
• Subjects: Biomedical and Life Sciences; Calcium; Cell Biology; Life Sciences; Proteins; Signal transduction; Stem cells
• ISSN: 1990-7478; 1990-7494
• DOI: 10.1134/S1990747813050085

By using Ca 2+ imaging and Fluo-4 dye, we examined the capability of certain agonists of G-protein coupled receptors to stimulate Ca 2+ signaling in cultured mesenchymal stromal cells (MSC) derived from the human adipose tissue. In particular, a small subpopulation (∼5%) MSC was found to respond to noradrenaline with Ca 2+ transients. The all-or-nothing fashion was characteristic of adrenergic Ca 2+ signaling in MSC, that is, while at low concentrations noradrenaline stimulated undetectable Ca 2+ transients, virtually maximal responses were elicited by this agonist at any concentration above the threshold of 100–200 nM. In some experiments, MSC were loaded with the photosensitive Ca 2+ chelator NP-EGTA to produce local or global jumps in cytosolic Ca 2+ concentration by virtue of Ca 2+ uncaging. Global uncaging eliciting a high enough Ca 2+ jump triggered a Ca 2+ transient in the MSC cytoplasm, which was similar to a noradrenaline response kinetically and by magnitude. When Ca 2+ uncaging was produced locally, it initiated a Ca 2+ signal that traveled along a cell with a speed that exceeded an expected one by two orders of magnitude, should Ca 2+ signal transfer be mediated merely by passive Ca 2+ diffusion in the presence of Ca 2+ buffer. These findings implicated Ca 2+ -induced Ca 2+ release (CICR) as a mechanism amplifying local Ca 2+ signals in MSC. Of Ca 2+ targets involved in CICR, the ryanodine receptor and IP 3 receptor are only known. The inhibitory analysis revealed IP 3 receptors to be principally responsible for CICR in MSC, whereas a contribution of ryanodine receptors was negligible. Altogether, our results suggest that an initial noradrenaline-dependent rise in cytosolic Ca 2+ stimulates, should it reach the threshold level, IP 3 receptors, thereby triggering an avalanche-like Ca 2+ release from Ca 2+ stores and underlying the all-or-nothing dependence of cellular responses on the agonist concentration.