biostudies-literatureUnknown32(3)Falcon DConsejería de Economía, Conocimiento, Empresas y Universidad, Junta de AndalucíaState Agency of ResearchThe upregulation of Orai1 and subsequent store-operated Ca²⁺ entry (SOCE) has been associated with adverse cardiac remodeling and heart failure (HF). However, the mechanism underlying Orai1 upregulation and its role in myocardial infarction remains unclear. Our study investigated the role of Orai1 in activating adenylyl cyclase 8 (AC8) and cyclic AMP (cAMP) response element-binding protein (CREB), as well as its contribution to cardiac dysfunction induced by ischemia and reperfusion (I/R). We found that I/R evoked an increase in the expression of Orai1 and AC8 in rats' hearts, resulting in a substantial rise in diastolic Ca²⁺ concentration ([Ca²⁺]_i), and reduced ventricular contractions. The expression of Orai1 and AC8 was also increased in ventrMolecular therapy : the journal of the American Society of Gene Therapy646-662https://www.ebi.ac.uk/biostudies/studies/S-EPMC10928147biostudies-literatureInhibition of adenylyl cyclase 8 prevents the upregulation of Orai1 channel, which improves cardiac function after myocardial infarction.PMC10928147Dominguez-Rodriguez AFalcon DGutierrez-Carretero ERosado JAMartin-Bornez MSmani TMayoral-Gonzalez IOrdonez-Fernandez ACalderon-Sanchez EMfalseInhibition of adenylyl cyclase 8 prevents the upregulation of Orai1 channel, which improves cardiac function after myocardial infarction.The upregulation of Orai1 and subsequent store-operated Ca²⁺ entry (SOCE) has been associated with adverse cardiac remodeling and heart failure (HF). However, the mechanism underlying Orai1 upregulation and its role in myocardial infarction remains unclear. Our study investigated the role of Orai1 in activating adenylyl cyclase 8 (AC8) and cyclic AMP (cAMP) response element-binding protein (CREB), as well as its contribution to cardiac dysfunction induced by ischemia and reperfusion (I/R). We found that I/R evoked an increase in the expression of Orai1 and AC8 in rats' hearts, resulting in a substantial rise in diastolic Ca²⁺ concentration ([Ca²⁺]_i), and reduced ventricular contractions. The expression of Orai1 and AC8 was also increased in ventr2024-01-01T00:00:00Z2024 Mar2025-04-04T10:42:12.389Z2025-04-04T10:42:12.389ZS-EPMC109281473829175510.1016/j.ymthe.2024.01.026