ABSTRACT
The Ca2+ wave is a chain reaction of intracellular Ca2+ release channels through a Ca2+-induced Ca2+ release mechanism. In cardiac myocytes, Ca2+ wave has drawn much attention because it is found to induce arrhythmia genesis. To investigate the microscopic process of wave propagation, Ca2+ imaging was performed with high spatial and temporal resolution via a laser-scanning confocal microscope combined with loose-seal patch clamp. These observation and analysis revealed that Ca2+ waves originated from a stochastic recruiting of Ca2+ release units (CRUs) by a pioneer Ca2+ spark, which had a low possibility in normal cells. During wave propagation, the 'waiting' time that the wave propagate between two neighboring CRUs along propagation direction distributed normally, and cells with a lower speed had a more dispersive distribution of 'waiting' time. To study the cause of the randomicity, the wave propagation was simulated with a numerical model. The simulation showed that the intrinsic stochastic open process of CRUs can fully explain the above phenomenon. Increasing the maximal open probability of CRUs reduced the randomness of wavefront propagation and enhanced the average velocity of wave meantime. These experimental and numerical results provided an unequivocal quantification for the stochastic behavior of wave initiation and propagation.