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

我们最近发现细胞外atp嘌呤受体信号在心肌细胞内Ca^<2+>振荡的细胞间同步中起着至关重要的作用。在这项研究中，我旨在阐明细胞外ATP和细胞内Mg^<2+>的浓度是否以及如何与培养的新生大鼠心肌细胞节律性收缩相关。同时测量荧光素-4荧光和荧光素/荧光素酶化学发光表明，心肌细胞内细胞外ATP浓度与细胞内Ca^<2+>浓度同步振荡，支持我们之前的推断，即细胞外ATP-嘌呤受体信号通路负责细胞内Ca^<2+>振荡的细胞间同步。此外，细胞内Mg^<2+>的浓度也随节律性收缩和细胞内Ca^<2+>的振荡而振荡，提示细胞内ATP的浓度随心肌细胞节律性收缩而变化。所有这些发现都导致了一种想法，即心肌细胞中多种非线性振荡的协调，如细胞内Ca^<2+> Mg^<2+>和ATP浓度的节律性变化，似乎对心脏的正常功能至关重要。

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.