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VASCULAR BIOLOGY

Behavior of Ca²⁺ waves in multicellular preparations from guinea pig ventricle

Departments of ¹Pharmacology and ²Cardiology, Juntendo University School of Medicine, Tokyo 113-8421, Japan

Submitted 26 April 2004 ; accepted in final form 7 August 2004

Ca⁺ waves have been implicated in Ca²⁺ overload-induced cardiac arrhythmias. To deepen understanding of the behavior of Ca²⁺ waves in a multicellular system, consecutive two-dimensional Ca²⁺ 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 Ca²⁺ waves were detected under the resting condition, whereas they were frequently observed during the rest immediately after high-frequency stimulations where cytoplasmic Ca²⁺ concentration and Ca²⁺ stored in the sarcoplasmic reticulum (SR) were gradually decreasing. The intervals of Ca²⁺ waves increased as they occurred later, their amplitudes and velocities remaining unchanged. A SERCA inhibitor reversibly prolonged the wave intervals. In Na⁺-free/Ca²⁺-free medium where neither Ca²⁺ influx nor Na⁺/Ca²⁺ exchange took place, recurrent Ca²⁺ 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 Ca²⁺ waves. Each cell independently exhibited its own regular rhythm of Ca²⁺ 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 Ca²⁺ waves at rest in normal Krebs solution, their propagation often was unidirectional, decreasing in frequency. In these cases, however, Ca²⁺ waves rarely moved beyond the cellular boundary. The gradient of the cytoplasmic Ca²⁺ concentration was suggested to be the cause of the one-way propagation.

wave propagation; luminal calcium ion; cytoplasmic calcium ion; sodium/calcium exchange

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