SPATIAL NONUNIFORMITIES IN [CA2-CONTRACTION COUPLING IN CARDIAC MYOCYTES(](I) DURING EXCITATION)

The intracellular calcium ([Ca2+](i)) transient in adult rat heart cel ls was examined using the fluorescent calcium indicator fluo-3 and a l aser scanning confocal microscope. We find that the electrically evoke d [Ca2+](i) transient does not rise at a uniform rate at all points wi thin the cell during the [Ca2+](i) transient. These spatial non-unifor mities in [Ca2+](i) are observed immediately upon depolarization and l argely disappear by the time the peak of the [Ca2+](i) transient occur s. Importantly, some of the spatial non-uniformity in [Ca2+](i) varies randomly in location from beat to beat. Analysis of the spatial chara cter of the non-uniformities suggests that they arise from the stochas tic nature of the activation of SR calcium-release channels. The non-u niformities in [Ca2+](i) are markedly enhanced by low concentrations o f Cd2+, suggesting that activation of L-type calcium channels is the p rimary source of activator calcium for the calcium transient. In addit ion, the pattern of calcium release in these conditions was very simil ar to the spontaneous calcium sparks that are observed under resting c onditions and which are due to spontaneous calcium release from the SR . The spatial non-uniformity in the evoked [Ca2+](i) transient under n ormal conditions can be explained by the temporal and spatial summatio n of a large number of calcium sparks whose activation is a stochastic process. The results are discussed with respect to a stochastic local control model for excitation-contraction (E-C) coupling, and it is pr oposed that the fundamental unit of E-C coupling consists of one dihyd ropyridine receptor activating a small group of ryanodine receptors (p ossibly four) in a square packing model.