title: Opening of mitochondrial ATP-sensitive potassium channels evokes oxygen radical generation in rabbit heart slices.
abstract: The purpose of this study was to determine whether ATP-sensitive potassium channel (K(ATP) channel) activation generates oxygen free radicals in the rabbit heart. We assayed malondialdehyde (MDA) in rabbit heart slices in vitro as an indicator of oxygen free radical generation. The K(ATP) channel openers, pinacidil and cromakalim, significantly increased MDA production in a concentration-dependent manner. MDA formation also increased linearly with incubation time in the presence of K(ATP) channel openers. The K(ATP) channel blockers, glibenclamide and 5-hydroxydecanoate (5-HD), decreased K(ATP) channel opener-induced MDA formation in a concentration-dependent manner. When Fe(2+) was administered to heart slices that had been pretreated with K(ATP) channel openers, a marked elevation in MDA was observed, compared to heart slices that were treated with Fe(2+) alone. A positive linear correlation between Fe(2+) and MDA level was observed. The MDA levels of heart slices subjected to anoxia for 15 min remained unchanged until reperfusion. When the heart slices were reoxygenated for 30 min, a marked increase in MDA formation was observed. However, in the presence of glibenclamide and 5-HD, reperfusion following anoxia did not result in increased MDA. These results suggest that the opening of mitochondrial K(ATP) channels in rabbit heart slices evokes oxygen free radical generation via a Fenton-type reaction.
authors: Department of Physiology & Biophysics, College of Medicine, Inje University, Busan, 613-735, Korea.
authors: Jin
authors: J
authors: Han
authors: Nari
authors: N
authors: Kim
authors: Juhee
authors: J
authors: Park
authors: Dae-Hyun
authors: DH
authors: Seog
authors: Hyun
authors: H
authors: Joo
authors: Euiyong
authors: E
authors: Kim
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D019806:Cromakalim / Q000494:pharmacology; D003652:Decanoic Acids / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005296:Ferrous Compounds / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D006880:Hydroxy Acids / Q000494:pharmacology; D007502:Iron Chelating Agents / Q000494:pharmacology; D016014:Linear Models; D008315:Malondialdehyde / Q000032:analysis; D008929:Mitochondria, Heart / Q000378:metabolism*; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism*; D020110:Pinacidil / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology*; D011817:Rabbits; D011930:Reaction Time / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D003652:Decanoic Acids; D005296:Ferrous Compounds; D006880:Hydroxy Acids; D007502:Iron Chelating Agents; D015221:Potassium Channels; D017382:Reactive Oxygen Species; D019806:Cromakalim; D008315:Malondialdehyde; C052853:5-hydroxydecanoic acid; D020110:Pinacidil; D000255:Adenosine Triphosphate; D005905:Glyburide