Cytosolic Ca²⁺ domain-dependent protective action of adenosine in cardiomyocytes

Recently, in beating cardiac cells heterogeneous spatiotemporal patterns in cytosolic Ca²⁺ distribution have been visualized, and associated with cell contraction. In non-beating cardiomyocytes, spatial heterogeneity of intracellular Ca²⁺ distribution has also been observed, yet its functional implication in resting cardiac cells is not known. Herein, distinct domains of lower versus higher concentrations of cytosolic Ca²⁺ (0.17 and 0.37 μM, respectively) were observed using epifluorescent digital imaging in single, non-beating, fluo-3-loaded cardiomyocytes. Extracellular K⁺ (16 mM) induced a uniform increase of cytosolic Ca²⁺, despite the initial presence of distinct domains of cytosolic Ca²⁺ (from 0.17 to 1.82 μM in domains with lower, and from 0.37 to 2.03 μM in domains with higher Ca²⁺ concentration, respectively). In contrast, adenosine (1 mM) prevented extracellular K⁺ to induce cytosolic Ca²⁺ loading selectively within domains with lower (from 0.17 to 0.18 μM), but not in domains with higher (from 0.37 to 1.4 μM) basal Ca²⁺ concentration. Thus, the response of a cardiomyocyte to the protective action of adenosine is heterogeneous within a resting single cell. The domain-distinct cytoprotective action of adenosine appears to be set by the basal Ca²⁺ concentration within a cytosolic domain.