title: 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.affiliation: Dipartimento di Farmacia, Università di Pisa, Via Bonanno, 6 I-56126 Pisa, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Testai
authors.forename: A
authors.initials: A
authors.lastname: Martelli
authors.forename: A
authors.initials: A
authors.lastname: Marino
authors.forename: V
authors.initials: V
authors.lastname: D'Antongiovanni
authors.forename: F
authors.initials: F
authors.lastname: Ciregia
authors.forename: L
authors.initials: L
authors.lastname: Giusti
authors.forename: A
authors.initials: A
authors.lastname: Lucacchini
authors.forename: S
authors.initials: S
authors.lastname: Chericoni
authors.forename: M C
authors.initials: MC
authors.lastname: Breschi
authors.forename: V
authors.initials: V
authors.lastname: Calderone
mesh_terms: D000818:Animals; D001794:Blood Pressure; D002118:Calcium / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology*; D044950:Flavanones / Q000494:pharmacology*; D017136:Ion Transport; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000819:agonists*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002316:Cardiotonic Agents; D044950:Flavanones; D051036:Large-Conductance Calcium-Activated Potassium Channels; C005273:naringenin; D011188:Potassium; D002118:Calcium