The activation of mitochondrial BK potassium channels contributes to the protective effects of naringenin against myocardial ischemia/reperfusion injury.

Abstract

Naringenin (NAR), flavonoid abundant in the genus Citrus, has been reported to interact with the large-conductance calcium-activated potassium channels (BK). Since activators of BK channels expressed in cardiac mitochondria trigger protective effects in several models of myocardial ischemia/reperfusion (I/R), this work aimed to evaluate the potential cardioprotective effects of NAR and the involvement of mitochondrial BK channels. In an in vivo model of acute infarct in rats, NAR (100mg/kg i.p.) significantly reduced the heart injury induced by I/R. This effect was antagonized by the selective BK-blocker paxilline (PAX). The cardioprotective dose of NAR did not cause significant effects on the blood pressure. In Largendorff-perfused rat hearts submitted to ischemia/reperfusion, NAR improved the post-ischemic functional parameters (left ventricle developed pressure and dP/dt) with lower extension of myocardial injury. On isolated rat cardiac mitochondria, NAR caused a concentration-dependent depolarization of mitochondrial membrane and caused a trans-membrane flow of thallium (potassium-mimetic cation). Both these effects were antagonized by selective blockers of BK channels. Furthermore, NAR half-reduced the calcium accumulation into the matrix of cardiac mitochondria exposed to high calcium concentrations. In conclusion, NAR exerts anti-ischemic effects through a "pharmacological preconditioning" that it is likely to be mediated, at least in part, by the activation of mitochondrial BK channels.

• Authors: L Testai, A Martelli, A Marino, V D'Antongiovanni, F Ciregia, L Giusti, A Lucacchini, S Chericoni, M C Breschi, V Calderone
• Journal: Biochemical pharmacology (Biochem Pharmacol) Vol. 85 Issue 11 Pg. 1634-43 (Jun 01 2013) ISSN: 1873-2968 [Electronic] England
• PMID: 23567997 (Publication Type: Journal Article)
• Copyright: Copyright © 2013. Published by Elsevier Inc.

Chemical References

• Cardiotonic Agents
• Flavanones
• Large-Conductance Calcium-Activated Potassium Channels
• naringenin
• Potassium
• Calcium

Topics

• Animals
• Blood Pressure
• Calcium (metabolism)
• Cardiotonic Agents (pharmacology)
• Flavanones (pharmacology)
• Ion Transport
• Large-Conductance Calcium-Activated Potassium Channels (agonists)
• Male
• Membrane Potential, Mitochondrial (drug effects)
• Mitochondria, Heart (drug effects, metabolism)
• Myocardial Reperfusion Injury (physiopathology, prevention & control)
• Potassium (metabolism)
• Rats
• Rats, Wistar