Alterations of Cardiac K_ATP Channels and Autophagy Contribute in the Late Cardioprotective Phase of Exercise Preconditioning

Abstract

The cardiac effects of exercise preconditioning (EP) are well established; however, the mechanisms involving cardiac ATP-sensitive potassium channel (K channel) subunits and autophagy are yet to be fully established. The present work aims to investigate the alterations of cardiac K channel subunits Kir6.2, SUR2A, and autophagy-related LC3 during the late cardioprotective phase of EP against exhaustive exercise-induced myocardial injury. Rats run on treadmill for four running time intervals, each with 10 minutes running and rest. Exhaustive exercise was performed 24 h after EP. Cardiac biomarkers, cTnI and NT-proBNP, along with the histological stain, were served as indicators of myocardial injury. Cardiac K channel subunits Kir6.2 and SUR2A were analyzed in this study, and autophagy was evaluated by LC3. The results revealed that EP reduced the exhaustive exercise-induced high level of serum cTnI and myocardial ischemia/hypoxia; however, it did not reveal any changes in the serum NT-proBNP level or cardiac BNP. Cardiac SUR2A mRNA significantly upregulated during the exhaustive exercise. The high levels of Kir6.2, SUR2A, LC3IIpuncta and LC3II turnover observed after exhaustive exercise were significantly mitigated by EP in the late phase. These results suggest that EP alleviates myocardial injury induced by exhaustive exercise through the downregulation of cardiac K channels and autophagy.

Everything in Moderation

“…Collectively, we understand that excessive exercise causes myocardial injury by dysregulating the autophagy machinery that can be reversed by precedent EP. 3) Although this study provides answers to several unsolved questions raised in previous investigations, a number of issues persist. 3) The first is the lack of solid evidence raised by the animal experimental model.…”

“…3) Although this study provides answers to several unsolved questions raised in previous investigations, a number of issues persist. 3) The first is the lack of solid evidence raised by the animal experimental model. To resolve this concern, the effect of KATP channel blockers in the heart in response to exhaustive exercise should be investigated.…”

“…6,7) Consistent with these results, Lu, et al demonstrated that the upregulation of KATP channels is accompanied by exhaustive-exercise-mediated acute myocardial injury. 3) They also observed that EP antecedent to exhaustive exercise markedly reduced Kir6.2 and SUR2A protein expressions. Furthermore, they found that the influence of EP on the SUR2A expression level is more significant than that for Kir6.2.…”

“…In this issue of International Heart Journal, Lu, et al revealed that the EP-mediated modulation of KATP channel expression and autophagy machinery alleviates exhaustiveexercise-induced myocardial damage. 3) The myocardial KATP channel consists of pore-forming Kir6.2 and regulatory SUR2A subunits. A growing body of evidence suggests that the KATP channel plays a critical role in protecting the myocardium against myocardial infarction by promoting IP.…”

“…Taken together, the results from Lu, et al suggest that opening of the cardiac KATP channels is protective, whereas overexpression of KATP channel subunits might be detrimental to the myocardium in response to exhaustive exercise, which could be alleviated by EP through the downregulation of SUR2A expression. 3) Autophagy is an evolutionally conserved catabolic process in which proteins and organelles are degraded in lysosomes. 8) Autophagy functions as a keeper of cellular homeostasis by eliminating intracellular waste and dangerous objects such as aggregated/denatured proteins and damaged organelles in the basal condition.…”