CYTOSOLIC CA2-DEPENDENT PROTECTIVE ACTION OF ADENOSINE IN CARDIOMYOCYTES( DOMAIN)

Recently, in beating cardiac cells heterogeneous spatiotemporal patter ns in cytosolic Ca2+ distribution have been visualized, and associated with cell contraction. In non-beating cardiomyocytes, spatial heterog eneity of intracellular Ca2+ distribution has also been observed, yet its functional implication in resting cardiac cells is not known. Here in, distinct domains of lower versus higher concentrations of cytosoli c Ca2+ (0.17 and 0.37 mu M, respectively) were observed using epifluor escent digital imaging in single, non-beating, fluo-3-loaded cardiomyo cytes. Extracellular K+ (16 mM) induced a uniform increase of cytosoli c 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 cytoso lic 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) basa l Ca2+ concentration. Thus, the response of a cardiomyocyte to the pro tective action of adenosine is heterogeneous within a resting single c ell. The domain-distinct cytoprotective action of adenosine appears to be set by the basal Ca2+ concentration within a cytosolic domain.