Coordination and dissociation of nonlinear oscillations in cardiomyocytes : dysfunction of holonic oscillators leading to arrhythmias

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We have recently found that the extracellular ATP-purinoceptor signaling is crucially involved in the intercellular synchronization of intracellular Ca^<2+> oscillations among cardiomyocytes. In this study, I aim at elucidating whether and how the concentrations of extracellular ATP and intracellular Mg^<2+> oscillate in association with rhythmic contraction of cultured cardiomyocytes from neonatal rats. The simultaneous measurement of the fluo-4 fluorescence and the luciferin/luciferase chemical luminescence showed that the concentration of extracellular ATP oscillated synchronously with the concentration of intracellular Ca^<2+> in cardiomyocytes, supporting our previous inference that the extracellular ATP-purinoceptor signaling is responsible for the intercellular synchronization of intracellular Ca^<2+> oscillations. In addition, the concentration of intracellular Mg^<2+> also oscillated in association with rhythmic contraction and intracellular Ca^<2+> oscillations, suggesting that the concentration of intracellular ATP varied depending on the rhythmic contraction of cardiomyocytes. All these findings have led to an idea that the coordination of multiple nonlinear oscillations in cardiomyocytes such as rhythmic variations in the concentrations of intracellular Ca^<2+> Mg^<2+> and ATP seems critical to the normal function of the heart.