2-aminoethoxydiphenylborane intervenes intracellular calcium signaling and attenuates myocardial ischemia-reperfusion injury in mice through ITPR1/MCU pathway.

Myocardial ischemia-reperfusion (MI/R) injury frequently occurs during the clinical management of ischemic heart disease. The underlying mechanism includes neutrophil infiltration, heightened intracellular Ca(2+) levels, mitochondrial energy metabolism disorder. This study investigated the pathological role of the inositol 1,4,5-trisphosphate receptor/mitochondrial calcium uniporter (ITPR1/MCU) pathway in regulating disturbances in intracellular calcium ([Ca(2+)](i)) and mitochondrial calcium ([Ca(2+)](m)) levels during MI/R injury. Furthermore, the study explored the potential of 2-aminoethoxydiphenylborane (2-APB) as a cardioprotective agent against MI/R injury. The outcomes of this investigation demonstrated that the ITPR1/MCU pathway was activated after MI/R, leading to [Ca(2+)](i)/[Ca(2+)](m) overload, impairing mitochondrial structure and function, and promoting cardiomyocyte death. The administered treatment attenuates myocardial injury after MI/R by reversing the [Ca(2+)](i)/[Ca(2+)](m) imbalance, maintaining cardiomyocyte mitochondrial homeostasis and promoting cardiomyocyte survival. Furthermore, the administration of 2-APB exerted a suppressive effect on MCU expression. Notably, the activation of MCU abolished the cardioprotective impact mediated by 2-APB. These results suggest that 2-APB intervenes [Ca(2+)](i)/[Ca(2+)](m) balance and maintains mitochondrial function through the ITPR1/MCU pathway. The strategic manipulation of this pathway holds promise as a prospective avenue for the clinical treatment of MI/R injury.