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 mu M, 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 mu M in domains with lower, and from 0.37 to 2.03 mu M 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 mu M), but not in domains with higher (from 0.37 to 1.4 mu M) 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.