Mitochondrial calcium uniporter mediates cardioprotection by remote preconditioning

The present study was to investigate the role of mitochondrial calcium uniporter (MCU) in cardioprotection by remote preconditioning and the possible underlying mechanisms. Remote preconditioning was induced in male SD rats by three cycles of 5 min of right femoral artery occlusion followed by 5 min of reperfusion. Myocardial ischemia–reperfusion (IR) was achieved by ligation of the left anterior descending coronary artery for 30 min and then reperfusion for 120 min. Infarct size and Levels of lactate dehydrogenase (LDH) in plasma were measured. The opening of the mitochondrial permeability transition pore (MPTP) was monitored with fluorescent calcein in isolated ventricular myocytes. Both remote preconditioning and ruthenium red (2.5mg/kg, i.v.), an inhibitor of MCU, significantly decreased the infarct size and plasma LDH level induced by IR, and these effects were attenuated by spermine (5mg/kg, i.v.), an activator of MCU, and atractyloside (5 mg/kg, i.v.), a MPTP activator. In isolated ventricular myocytes loaded with calcein, ruthenium red (5 μmol/L) decreased MPTP opening induced by calcium (200 μmol/L), and this effect was attenuated by cotreatment with spermine (20 μmol/L) or atractyloside (20 μmol/L). The results indicate that inhibition of MCU is involved in the cardioprotection induced by remote preconditioning, and MPTP may be the downstream of MCU. (Supported by ZJSTB grant No. 2006C33070)