Subcellular calcium signalling in cardiac cells revealed with fast two-dimensional confocal imaging

Excitation-contraction (e-c) coupling in atrial myocytes was studied with fast confocal microscopy and simultaneous Ca2+-current (I-Ca) measurements. Cat atrial myocytes lack transverse tubules and contain junctional (j-SR) and non junctional SR (nj-SR) which both have ryanodine receptor Ca2+ release channels. I-Ca triggered Ca2+ release from discrete peripheral j-SR release sites; which then fused into a peripheral 'ring' of elevated [Ca2+](i), followed by propagation (via Ca2+-induced Ca2+ release, CICR) to the center and contraction. j-SR Ca2+ release could be terminated instantaneously by interrupting I-Ca, whereas nj-SR Ca2+ release continued, once initiated, even after ICa and j-SR Ca2+ release were terminated. Resting myocytes exhibited spontaneous Ca2+ release events including Ca2+ sparks and local or global Ca2+-waves. Local Ca2+-waves, which propagated in a saltatory fashion along the sarcolemma ('coupled' Ca2+ sparks), and global Ca2+-waves revealed the sequential activation of individual SR Ca2+ release sites. In summary, during e-c coupling in atrial cells the elevation of [Ca2+](i) begins with j-SR Ca2+ release under the tight control of I-Ca. The peripheral increase of [Ca2+](i) subsequently activates adjacent nj-SR resulting in centripetal propagation of activation via CICR.