Mesenchymal stromal cells (MSCs) from different sources represent a heterogeneous population of proliferating non-differentiated cells that contains multipotent stem cells capable of originating a variety of mesenchymal cell lineages. By using Ca2+ imaging and the Ca2+ dye Fluo-4, we studied MSCs from the human adipose tissue and examined Ca2+ signaling initiated by purinergic agonists. Although all tested compounds were capable of mobilizing intracellular Ca2+ in MSCs, sensitivity of individual MSCs to a particular agonist varied from cell to cell. Being characterized by a relative change of Fluo-4 fluorescence, agonist-induced Ca2+ responses were generated in an “all-or-nothing” fashion. Specifically, at relatively low doses, agonists elicited undetectable responses but initiated quite similar Ca2+ transients of large magnitude at all concentrations above the threshold, which was nearly 0.1, 0.2, 0.5, 1, and 2 µM for noradrenaline, ADP, ATP, and UTP, respectively. The inhibitory analysis and Ca2+/IP3 uncaging pointed at the phosphoinositide cascade as a pivotal pathway responsible for agonist transduction and implicated Ca2+-induced Ca2+ release (CICR) mediated by IP3 receptors in shaping agonists-dependent Ca2+ signals. Altogether, our data suggest that agonist transduction in MSCs includes two fundamentally different stages: an agonist initially triggers a local, gradual, and relatively small Ca2+ signal, which next stimulates CICR to accomplish transduction with a large and global Ca2+ transient. By involving the trigger-like mechanism CICR, a cell is capable of generating Ca2+ responses of virtually universal shape and magnitude at different agonist concentrations above the threshold.
Ca2+ signaling, G-protein coupled receptors, calcium-induced calcium release, IP3 receptors, mesenchymal stromal cells
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