title: [New fluorine-containing openers of ATP-sensitive potassium channels flokalin and tioflokalin inhibit calcium-induced mitochondrial pore opening in rat hearts].
abstract: In experiments in vitro on the mitochondria isolated from the rat's heart we studied the effects of the openers of ATP-sensitive potassium channels (K(ATP)-channels), flocalin and tioflocalin, on the calcium-induced mitochondrial pore (MPTP) opening. Flocalin and tioflocalin caused moderate Ca(2+)-independent mitochondria swelling, which was prevented by a specific inhibitor of 5-hydroxydecanoate. This allowed to identify these compounds as mitochondrial K(ATP)-channels openers. We found that concentration-dependent inhibitory effects (10(-7) to 10(-4) M) of flocalin (with IC50 = 50 microM) and tioflocalin (with IC50 = 2,7 microM) on Ca(2+)-induced mitochondrial swelling (MPTP opening) in the heart characterized more powerful cardioprotective action of the latter. It was shown that the administration of these compounds in experiments in vivo decreased the sensitivity of the MPTP opening to Ca2+. Thus, under physiological conditions the activators K(ATP)-channels probably provide the membrane-stabilizing effects, thereby effectively increasing the organelles resistance to Ca2+, an inductor of MPTP. The results obtained allowed to characterize the role of the compound studied as cardioprotectors and regulators of the MPTP formation in the heart, indicated their anti-ischemic and anti-apoptotic effects that can be used in order to correct the mitochondrial dysfunction under pathological conditions of the cardiovascular system.
authors.forename: N A
authors.initials: NA
authors.lastname: Strutyns'ka
authors.forename: R B
authors.initials: RB
authors.lastname: Strutyns'kyĭ
authors.forename: S V
authors.initials: SV
authors.lastname: Chorna
authors.forename: O M
authors.initials: OM
authors.lastname: Semenykhina
authors.forename: L A
authors.initials: LA
authors.lastname: Mys'
authors.forename: O O
authors.initials: OO
authors.lastname: Moĭbenko
authors.forename: V F
authors.initials: VF
authors.lastname: Sahach
mesh_terms: D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects*; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism; D008933:Mitochondrial Swelling / Q000187:drug effects; D020110:Pinacidil / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002316:Cardiotonic Agents; C559719:N-(4-difluoromethoxyphenyl)-N'-pinacolyl-N''-cyanoguanidine; D015221:Potassium Channels; C117780:mitochondrial K(ATP) channel; D020110:Pinacidil; D002118:Calcium