表題番号：2024R-024
日付：2024/10/22
研究課題自律拍動心筋細胞集団の散逸力と揺動力の拮抗がもたらす非対称な秩序形成の機構の理解
| 研究者所属（当時） | 資格 | 氏名 | |
|---|---|---|---|
| （代表者） | 理工学術院 先進理工学部 | 教授 | 安田 賢二 |
- 研究成果概要
- As the community effect of cells was neglected in the conventional single cell-based in vitro screening, the potential difference in results caused by the cell number and their spatial arrangement differences has not yet been evaluated sufficiently. Here, we have investigated the effect of the difference in community size and spatial arrangement for cardiomyocyte network response against proarrhythmic compounds. We compared the responses against the proarrhythmic compound, E-4031, using three different types of cell networks of cardiomyocytes: small sheet, large square sheet, and large closed-loop sheet, which were formed in agarose microchambers fabricated on a multielectrode array chip. The beating frequency in large square and closed-loop sheets was maintained stable even when exposed to a high dose (100 nM) of E-4031. In contrast, small sheets that have fluctuated beating in the original state acquired stable beating when administering a medium dose (10 nM) of E-4031 caused by the antiarrhythmic efficacy. The repolarization index, field potential duration (FPD), was prolonged in closed-loop sheets with a 10 nM concentration of E-4031, even though small and large sheets did not show a noticeable effect at this concentration. Hence, only the closed-loop structure cardiomyocyte networks showed significant prolongation of FPD during hERG ion channel blocking compared to the other two network patterns. On the other hand, FPDs of large sheets were the most durable against the administration of E-4031 among the three geometries of cardiomyocyte networks. The results suggest that the spatial arrangement of the cardiomyocyte network can collectively dominate the function of the component cell’s ion channels under the administration of proarrhythmic compounds despite the network being constructed of homogeneous cells.