Hierarchical Correlation Dynamics among Cellular Rhythms: Coordination and Dissociation of Non-linear Biological Oscillators.

生物系统中存在许多节律现象。在细胞水平上也观察到细胞内钙离子浓度的周期性变化等多种振荡现象。本研究旨在阐明细胞振荡节律之间相互作用的机制，以及这些细胞节律的协调和解离。结果如下：1.在4DIV培养的心肌细胞中，与自发性节律性收缩相关的细胞内游离钙离子浓度的周期性变化(钙振荡)在肌细胞之间是同步的。培养的心肌细胞内钙振荡也是同步的，彼此之间没有明显的物理接触。即使用缝隙连接通道阻断剂DSA或庚醇阻断细胞间的缝隙连接通讯，细胞内钙振荡的同步性仍持续存在。当心肌细胞的节律性收缩被BDM(一种E-C偶联的解偶联剂)几乎完全终止时，这种同步性也持续了下来。用P2-嘌呤受体阻断剂苏拉明处理培养的心肌细胞，可导致心肌细胞内钙振荡的异步化。综上所述，上述研究结果提示，细胞外ATP-嘌呤受体信号系统参与了培养心肌细胞内钙振荡的同步化。此外，心肌细胞-成纤维细胞共培养分析表明，与心肌细胞共培养的心脏成纤维细胞通过缝隙连接增强了心肌细胞之间的细胞间通讯，从而稳定了培养的心肌细胞的自发收缩节律。

There are many rhythmic phenomena in the biological system. A variety of oscillatory phenomena such as a cyclic change in the concentration of intracellular Ca2+ are also observed in the cellular level. The present study aims at elucidating the mechanisms responsible for interactions among cellular oscillatory rhythms, and for the coordination and dissociation of such cellular rhythms. The results are summarized as follows:1. In cultured cardiac myocytes at 4 DIV, the cyclic changes in the concentration of intracellular free Ca2+ (Ca2+ oscillation) in association with spontaneous rhythmic contractions were synchronized among myocytes.2. The intracellular Ca2+ oscillations were also synchronized among cultured cardiac myocytes without apparent physical contact with each other.3. The synchronization of Ca2+ oscillation was persisted even when gap junctional intercellular communication was blocked by treatment with either DSA or heptanol, blockers of gap junction channels. The synchronization was also persisted when the rhythmic contraction of cardiac myocytes was almost perfectly terminated by treatment with BDM, an uncoupler of E-C coupling.4. Treatment of cultured cardiac myocytes with suramin, a blocker of P2-purinoceptors, resulted in the asynchronization of intracellular Ca2+ oscillations among myocytes.5. Taken together, above findings have led to a suggestion that the extracellular ATP-purinoceptor signaling system is involved in the synchronization of intracellular Ca2+ oscillations among cultured cardiac myocytes.6. In addition, analysis using cardiac myocytes-fibroblast co-cultures demonstrated that cardiac fibroblasts co-cultured with cardiac myocytes enhanced the intercellular communication among myocytes via gap junctions, thereby stabilizing the spontaneous contraction rhythm of cultured cardiac mvocvtes.