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Article: Functional roles of cardiac and vascular ATP-sensitive potassium channels clarified by Kir6.2-knockout mice

TitleFunctional roles of cardiac and vascular ATP-sensitive potassium channels clarified by Kir6.2-knockout mice
Authors
KeywordsChemicals And Cas Registry Numbers
Issue Date2001
PublisherLippincott Williams & Wilkins. The Journal's web site is located at http://circres.ahajournals.org
Citation
Circulation Research, 2001, v. 88 n. 6, p. 570-577 How to Cite?
AbstractATP-sensitive potassium (K ATP) channels were discovered in ventricular cells, but their roles in the heart remain mysterious. K ATP channels have also been found in numerous other tissues, including vascular smooth muscle. Two pore-forming subunits, Kir6.1 and Kir6.2, contribute to the diversity of K ATP channels. To determine which subunits are operative in the cardiovascular system and their functional roles, we characterized the effects of pharmacological K + channel openers (KCOs, ie, pinacidil, P-1075, and diazoxide) in Kir6.2-deficient mice. Sarcolemmal K ATP channels could be recorded electrophysiologically in ventricular cells from Kir6.2 +/+ (wild-type [WT]) but not from Kir6.2 -/- (knockout [KO]) mice. In WT ventricular cells, pinacidil induced an outward current and action potential shortening, effects that were blocked by glibenclamide, a K ATP channel blocker. KO ventricular cells exhibited no response to KCOs, but gene transfer of Kir6.2 into neonatal ventricular cells rescued the electrophysiological response to P-1075. In terms of contractile function, pinacidil decreased force generation in WT but not KO hearts. Pinacidil and diazoxide produced concentration-dependent relaxation in both WT and KO aortas precontracted with norepinephrine. In addition, pinacidil induced a glibenclamide-sensitive current of similar magnitude in WT and KO aortic smooth muscle cells and comparable levels of hypotension in anesthetized WT and KO mice. In both WT and KO aortas, only Kir6.1 mRNA was expressed. These findings indicate that the Kir6.2 subunit mediates the depression of cardiac excitability and contractility induced by KCOs; in contrast, Kir6.2 plays no discernible role in the arterial tree.
Persistent Identifierhttp://hdl.handle.net/10722/91479
ISSN
2015 Impact Factor: 11.551
2015 SCImago Journal Rankings: 5.755
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorSuzuki, Men_HK
dc.contributor.authorLi, RAen_HK
dc.contributor.authorMiki, Ten_HK
dc.contributor.authorUemura, Hen_HK
dc.contributor.authorSakamoto, Nen_HK
dc.contributor.authorOhmotoSekine, Yen_HK
dc.contributor.authorTamagawa, Men_HK
dc.contributor.authorOgura, Ten_HK
dc.contributor.authorSeino, Sen_HK
dc.contributor.authorMarbán, Een_HK
dc.contributor.authorNakaya, Hen_HK
dc.date.accessioned2010-09-17T10:20:05Z-
dc.date.available2010-09-17T10:20:05Z-
dc.date.issued2001en_HK
dc.identifier.citationCirculation Research, 2001, v. 88 n. 6, p. 570-577en_HK
dc.identifier.issn0009-7330en_HK
dc.identifier.urihttp://hdl.handle.net/10722/91479-
dc.description.abstractATP-sensitive potassium (K ATP) channels were discovered in ventricular cells, but their roles in the heart remain mysterious. K ATP channels have also been found in numerous other tissues, including vascular smooth muscle. Two pore-forming subunits, Kir6.1 and Kir6.2, contribute to the diversity of K ATP channels. To determine which subunits are operative in the cardiovascular system and their functional roles, we characterized the effects of pharmacological K + channel openers (KCOs, ie, pinacidil, P-1075, and diazoxide) in Kir6.2-deficient mice. Sarcolemmal K ATP channels could be recorded electrophysiologically in ventricular cells from Kir6.2 +/+ (wild-type [WT]) but not from Kir6.2 -/- (knockout [KO]) mice. In WT ventricular cells, pinacidil induced an outward current and action potential shortening, effects that were blocked by glibenclamide, a K ATP channel blocker. KO ventricular cells exhibited no response to KCOs, but gene transfer of Kir6.2 into neonatal ventricular cells rescued the electrophysiological response to P-1075. In terms of contractile function, pinacidil decreased force generation in WT but not KO hearts. Pinacidil and diazoxide produced concentration-dependent relaxation in both WT and KO aortas precontracted with norepinephrine. In addition, pinacidil induced a glibenclamide-sensitive current of similar magnitude in WT and KO aortic smooth muscle cells and comparable levels of hypotension in anesthetized WT and KO mice. In both WT and KO aortas, only Kir6.1 mRNA was expressed. These findings indicate that the Kir6.2 subunit mediates the depression of cardiac excitability and contractility induced by KCOs; in contrast, Kir6.2 plays no discernible role in the arterial tree.en_HK
dc.languageengen_HK
dc.publisherLippincott Williams & Wilkins. The Journal's web site is located at http://circres.ahajournals.orgen_HK
dc.relation.ispartofCirculation Researchen_HK
dc.subjectChemicals And Cas Registry Numbersen_HK
dc.subject.meshAdenosine Triphosphate - pharmacology - physiologyen_HK
dc.subject.meshAdenoviridae - geneticsen_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshAorta - drug effects - physiologyen_HK
dc.subject.meshBlood Pressure - drug effectsen_HK
dc.subject.meshBlotting, Northernen_HK
dc.subject.meshDiazoxide - pharmacologyen_HK
dc.subject.meshDose-Response Relationship, Drugen_HK
dc.subject.meshElectrophysiologyen_HK
dc.subject.meshGenetic Vectors - geneticsen_HK
dc.subject.meshGenotypeen_HK
dc.subject.meshGlyburide - pharmacologyen_HK
dc.subject.meshHeart - drug effects - physiologyen_HK
dc.subject.meshHeart Rate - drug effectsen_HK
dc.subject.meshHeart Ventricles - cytology - drug effectsen_HK
dc.subject.meshMembrane Potentials - drug effectsen_HK
dc.subject.meshMiceen_HK
dc.subject.meshMice, Inbred C57BLen_HK
dc.subject.meshMice, Knockouten_HK
dc.subject.meshMuscle, Smooth, Vascular - cytology - drug effects - physiologyen_HK
dc.subject.meshNorepinephrine - pharmacologyen_HK
dc.subject.meshPinacidil - pharmacologyen_HK
dc.subject.meshPotassium Channels - drug effects - genetics - physiologyen_HK
dc.subject.meshPotassium Channels, Inwardly Rectifyingen_HK
dc.subject.meshRNA, Messenger - genetics - metabolismen_HK
dc.subject.meshTransfectionen_HK
dc.subject.meshVasoconstriction - drug effectsen_HK
dc.subject.meshVasodilator Agents - pharmacologyen_HK
dc.subject.meshVentricular Functionen_HK
dc.titleFunctional roles of cardiac and vascular ATP-sensitive potassium channels clarified by Kir6.2-knockout miceen_HK
dc.typeArticleen_HK
dc.identifier.emailLi, RA:ronaldli@hkucc.hku.hken_HK
dc.identifier.authorityLi, RA=rp01352en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.pmid11282890en_HK
dc.identifier.scopuseid_2-s2.0-0035970590en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0035970590&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume88en_HK
dc.identifier.issue6en_HK
dc.identifier.spage570en_HK
dc.identifier.epage577en_HK
dc.identifier.isiWOS:000167821400007-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridSuzuki, M=7406960495en_HK
dc.identifier.scopusauthoridLi, RA=7404724466en_HK
dc.identifier.scopusauthoridMiki, T=7401680016en_HK
dc.identifier.scopusauthoridUemura, H=35473578700en_HK
dc.identifier.scopusauthoridSakamoto, N=55183117000en_HK
dc.identifier.scopusauthoridOhmotoSekine, Y=6506484685en_HK
dc.identifier.scopusauthoridTamagawa, M=7005691165en_HK
dc.identifier.scopusauthoridOgura, T=7402985338en_HK
dc.identifier.scopusauthoridSeino, S=23390248600en_HK
dc.identifier.scopusauthoridMarbán, E=8075977300en_HK
dc.identifier.scopusauthoridNakaya, H=7102874552en_HK

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