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

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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.