RT Journal Article SR Electronic T1 Acid sensing ion channel 1a is a key mediator of cardiac ischemia-reperfusion injury JF bioRxiv FD Cold Spring Harbor Laboratory SP 869826 DO 10.1101/869826 A1 Meredith A. Redd A1 Sarah E. Scheuer A1 Natalie J. Saez A1 Ling Gao A1 Mark Hicks A1 Jeanette E. Villanueva A1 Melissa E. Reichelt A1 Jason N. Peart A1 Louise E. See Hoe A1 Han S. Chiu A1 Xiaoli Chen A1 Yuliangzi Sun A1 Jacky Y. Suen A1 Robert J Hatch A1 Ben Rollo A1 Mubarak A.H. Alzubaidi A1 Snezana Maljevic A1 Greg A. Quaife-Ryan A1 Walter G. Thomas A1 James E. Hudson A1 Enzo R. Porrello A1 Gabriel Cuellar-Partida A1 John F. Fraser A1 Steven Petrou A1 Glenn F. King A1 Peter S. Macdonald A1 Nathan J. Palpant YR 2020 UL http://biorxiv.org/content/early/2020/11/17/869826.abstract AB The proton-gated acid-sensing ion channel 1a (ASIC1a) is implicated in the injury response to cerebral ischemia but little is known about its role in cardiac ischemia. We provide genetic evidence that ASIC1a is involved in myocardial ischemia-reperfusion injury (IRI) and show that pharmacological inhibition of ASIC1a yields robust cardioprotection in rodent and human models of cardiac ischemia, resulting in improved post-IRI cardiac viability and function. Consistent with a key role for ASIC1a in cardiac ischemia, we show that polymorphisms in the ASIC1 genetic locus are strongly associated with myocardial infarction. Collectively, our data provide compelling evidence that ASIC1a is a key target for cardioprotective drugs to reduce the burden of disease associated with myocardial ischemia.Competing Interest StatementThe authors have declared no competing interest.