Abstract
BackgroundsTo clarify the role of cardiac fibroblasts in beating synchronization, we have made simple lined-up cardiomyocyte-fibroblast network model in an on-chip single-cell-based cultivation system.ResultsThe synchronization phenomenon of two cardiomyocyte networks connected by fibroblasts showed (1) propagation velocity of electrophysiological signals decreased a magnitude depending on the increasing number of fibroblasts, not the lengths of fibroblasts; (2) fluctuation of interbeat intervals of the synchronized two cardiomyocyte network connected by fibroblasts did not always decreased, and was opposite from homogeneous cardiomyocyte networks; and (3) the synchronized cardiomyocytes connected by fibroblasts sometimes loses their synchronized condition and recovered to synchronized condition, in which the length of asynchronized period was shorter less than 30 beats and was independent to their cultivation time, whereas the length of synchronized period increased according to cultivation time.ConclusionsThe results indicated that fibroblasts can connect cardiomyocytes electrically but do not significantly enhance and contribute to beating interval stability and synchronization. This might also mean that an increase in the number of fibroblasts in heart tissue reduces the cardiomyocyte 'community effect', which enhances synchronization and stability of their beating rhythms.
Highlights
Cardiomyocytes make up more than half the volume of normal heart tissue and play a role in the pumping of blood
Using that system to examine the contribution of the ‘community effect’ to the stability of the beating in the homogeneous cardiomyocyte networks [20,21], we found that the beating of an in vitro community comprising nine cells is as stable as the beating of the heart, that the rhythms of two isolated cells became synchronized after the cells made physical contact with each other, and that the synchronized rhythm of those two cells was the more stable one rather than the faster one [22]
We cultivated single fibroblasts to connect isolated two cardiomyocytes cultivated in both sides of three lined-up microchambers so that we could see how two cardiomyocytes with different beating rhythms synchronized their rhythms through fibroblasts
Summary
Cardiomyocytes make up more than half the volume of normal heart tissue and play a role in the pumping of blood. Fibroblasts are more plentiful in diseased hearts than healthy hearts, so one must consider the possibility that electrical coupling between fibroblasts and cardiomyocytes plays a role in arrhythmogenesis [1,2,3] It has, been shown in cell culture that the electrical coupling of fibroblasts can propagate the contraction among cardiomyocytes [4,5,6,7]. The measurement of electrical coupling between fibroblasts and cardiomyocytes was not considered as the single fibroblast’s electrical coupling function. To overcome these problems, we developed an agarose microchamber system by using the photothermal etching method [13,14]. Examine the role of the community effect in heterogeneous cell networks, especially in cardiomyocytes
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