Initiation and development of calcium waves in rat myocytes

To understand the characteristics of asynchrony in spontaneously occurring increases in cytoplasmic calcium concentrations ([Ca²⁺](i)) in the cardiac myocyte, we observed newly developed changes in regional [Ca²⁺](i) after a physical injury to the sarcolemma. Myocytes were isolated from rat left ventricle and loaded with acetoxymethyl ester of fura-2. We analyzed dynamic changes in fluorescence images by video densitometry. After the injury was imposed, three types of responses were observed: 1) rapid contracture with steady increase in [Ca²⁺](i); 2) periodic development of a calcium wave; and 3) quiescence after the injury. In some myocytes with the second type of response, a sustained burst of calcium waves was observed. In myocytes in which multiple calcium waves are present simultaneously, a propagated wave can reset a cycle of wave generation at the wave focus. Waves disappear after their collision, which indicates the existence of a refractory period after the calcium transient. The wave originating from the focus with the fastest frequency dominates the whole cell. Thus dynamic changes in regional [Ca²⁺](i) are asynchronous but are organized by the following principles: 1) a regional increase in [Ca²⁺](i) can propagate; 2) a propagated calcium wave can reset a cycle of wave initiation at the focus; and 3) a regional calcium transient leaves a refractory period.