論文 - 詳細
| RRC ID | 83603 |
|---|---|
| 著者 | Hinata Y, Sasaki D, Matsuura K, Shimizu T. |
| タイトル | Induction of cardiac alternans in human iPS-derived cardiomyocytes through β-adrenergic receptor stimulation. |
| ジャーナル | Physiol Rep |
| Abstract |
Cardiac alternans (C-ALT) is a phenomenon of alternating strong and weak contractions in the heart and is considered a risk factor for the development of heart failure and arrhythmias. However, no model has been reported that can induce C-ALT in vitro using human cells, and the developmental mechanism of C-ALT has not been studied using human cells. In this study, we successfully induced C-ALT in vitro using human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). By stimulating β-adrenergic receptor with isoproterenol on hiPSC-CMs cultured in atmospheric condition (with ~0.04% CO2), contractility and calcium transient were observed to alternately increase and decrease with each beat. In contrast, C-ALT was not induced in hiPSC-CMs cultured at 5% CO2 concentration. Since previous studies have linked C-ALT to problems with calcium regulation in the sarcoplasmic reticulum (SR), we exposed hiPSC-CMs to compounds that alter SR Ca2+ loading and analyzed their contractile responses. The results showed that exposure to verapamil, thapsigargin, and ryanodine either suppressed or eliminated C-ALT. In contrast, omecamtiv mecarbil and blebbistatin, which alter contractility without SR Ca2+ loading, did not induce or suppress C-ALT. These results suggest that C-ALT in hiPSC-CMs induced by isoproterenol may be due to abnormal regulation of the ryanodine receptor's opening and closing caused by excessive Ca2+ load in the SR from β-adrenergic receptor stimulation. |
| 巻・号 | 12(24) |
| ページ | e70152 |
| 公開日 | 2024-12-1 |
| DOI | 10.14814/phy2.70152 |
| PMID | 39715724 |
| PMC | PMC11666346 |
| MeSH | Adrenergic beta-Agonists* / pharmacology Arrhythmias, Cardiac / chemically induced Arrhythmias, Cardiac / metabolism Arrhythmias, Cardiac / physiopathology Calcium / metabolism Calcium Signaling / drug effects Cells, Cultured Humans Induced Pluripotent Stem Cells* / cytology Induced Pluripotent Stem Cells* / drug effects Induced Pluripotent Stem Cells* / metabolism Isoproterenol* / pharmacology Myocardial Contraction / drug effects Myocytes, Cardiac* / drug effects Myocytes, Cardiac* / metabolism Myocytes, Cardiac* / physiology Receptors, Adrenergic, beta* / metabolism Sarcoplasmic Reticulum / drug effects Sarcoplasmic Reticulum / metabolism |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | 201B7(HPS0063) |