Behavior of Ca(2+) waves in multicellular preparations from guinea pig ventricle

Ca(+) waves have been implicated in Ca(2+) overload-induced cardiac arrhythmias. To deepen understanding of the behavior of Ca(2+) waves in a multicellular system, consecutive two-dimensional Ca(2+) images were obtained with a confocal microscope from surface cells of guinea pig ventricular papillary muscles loaded with fluo 3 or rhod 2. In intact muscles, no Ca(2+) waves were detected under the resting condition, whereas they were frequently observed during the rest immediately after high-frequency stimulations where cytoplasmic Ca(2+) concentration and Ca(2+) stored in the sarcoplasmic reticulum (SR) were gradually decreasing. The intervals of Ca(2+) waves increased as they occurred later, their amplitudes and velocities remaining unchanged. A SERCA inhibitor reversibly prolonged the wave intervals. In Na(+)-free/Ca(2+)-free medium where neither Ca(2+) influx nor Na(+)/Ca(2+) exchange took place, recurrent Ca(2+) waves emerged at constant intervals in each cell. These results are consistent with the conclusion that the loading level of the SR is critical for induction of Ca(2+) waves. Each cell independently exhibited its own regular rhythm of Ca(2+) wave with a distinct interval. These waves propagated in either direction along the longitudinal axis within a muscle cell, but seldom beyond the cell boundary. In contrast, in partially damaged muscles that showed spontaneous Ca(2+) waves at rest in normal Krebs solution, their propagation often was unidirectional, decreasing in frequency. In these cases, however, Ca(2+) waves rarely moved beyond the cellular boundary. The gradient of the cytoplasmic Ca(2+) concentration was suggested to be the cause of the one-way propagation.