マツウラ　カツヒサ   MATSUURA Katsuhisa   松浦　勝久    所属   医学部 医学科    職種   教授・基幹分野長
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Induction of cardiac alternans in human iPS-derived cardiomyocytes through β-adrenergic receptor stimulation.
掲載誌名	正式名：Physiological reports 略　 称：Physiol Rep ISSNコード：2051817X/2051817X
掲載区分	国外
巻・号・頁	12(24),pp.e70152
著者・共著者	HINATA Yuto†, SASAKI Daisuke, MATSUURA Katsuhisa*, SHIMIZU Tatsuya*
発行年月	2024/12
概要	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.
DOI	10.14814/phy2.70152
PMID	39715724