BK CHANNEL ACTIVATION INDUCES MITOCHONDRIAL MAINTENANCE AFTER HYPOXIA/REOXYGENATION

Ischemic heart disease remains a significant cause of mortality globally. When a myocardial infarction occurs, the reduction or interruption of blood flow leads to an imbalance between the supply and demand of oxygen in the affected area. Restoring blood flow promptly through reperfusion is crucial for the survival of the heart muscle. However, it is worth noting that reperfusion itself can cause injury to the myocardium. In recent research, the cardioprotective potential of an agonist of the large-conductance calcium-activated potassium channel (BK channel) has been explored. The BK channel is involved in regulating vascular tone, cardiac contractility, and ischemic preconditioning, which are all important factors in myocardial protection. The present study aims to investigate the mechanisms of cardioprotection conferred by BK channel activation, focusing on the effects on the maintenance of mitochondrial function. For this study, a total of 14 animals were involved, protocol CEUA number 119/21, 4-week-old male C57BL/6 mice, with 25-30 grams, were euthanized by cervical dislocation. Hearts were quickly removed and mitochondria were isolated by a differential centrifugation method. Immediately after isolation, mitochondrial function was evaluated by measurement of O² consumption in different respiratory states, ATP production, ROS production, and transmembrane potential. The mitochondria isolated from fresh hearts were incubated directly with BK channel agonist and subjected to hypoxia/reoxygenation in vitro. Incubation of BK channel agonist in mitochondria subjected to hypoxia and reoxygenation prevented reductions in mitochondrial respiration (102.2±8.3), ATP production (211.2±4.3), and reduced mitochondrial ROS production (278.3±11.0) compared to the group subjected to hypoxia/reoxygenation (42.5±3.0; 167±41.2; 341.0±4.4; p<0.001, respectively). BK channel activation can protect mitochondria function against hypoxia/reoxygenation injury.