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Article: Adenosine-induced activation of ATP-sensitive K + channels in excised membrane patches is mediated by PKC

TitleAdenosine-induced activation of ATP-sensitive K + channels in excised membrane patches is mediated by PKC
Authors
Issue Date1999
PublisherAmerican Physiological Society. The Journal's web site is located at http://intl-ajpheart.physiology.org/
Citation
American Journal Of Physiology - Heart And Circulatory Physiology, 1999, v. 276 n. 2 45-2, p. H488-H495 How to Cite?
AbstractBoth protein kinase C (PKC) and adenosine receptor activation have been shown to enhance ATP-sensitive K + (K(ATP)) channels. The present studies were designed to determine whether PKC mediates adenosine effects on the K(ATP) channel. The dependence of K(ATP) channel activity (nP(o)) on intracellular ATP concentration ([ATP](i)) was determined in excised rabbit ventricular membrane patches. External adenosine (100 μM in the pipette solution) significantly increased K(ATP) nP(o) at all [ATP](i) between 5 and 50 μM by decreasing channel sensitivity to [ATP](i) (dissociation constant increased from 7.4 ± 0.8 to 22.2 ± 3.1 μM, P < 0.001), an effect blocked by the adenosine receptor antagonist 8-phenyltheophylline (10 μM). When the highly selective PKC blocker bisindolylmaleimide (BIM) was included in the internal (bath) solution, the K(ATP)-stimulating action of adenosine was prevented. The addition of BIM to the superfusate rapidly inhibited K(ATP) channels activated by adenosine. Endogenous PKC activation by phorbol 12,13- didecanoate (PDD), but not administration of the inactive congener 4α-PDD, enhanced K(ATP) activity. Internal guanosine 5'-O-(2-thiodiphosphate) prevented K(ATP) activation by adenosine, an effect which could be overridden by exposure to PDD. We conclude that PKC mediates adenosine activation of K(ATP) channels in excised membrane patches in a membrane-delimited fashion.
Persistent Identifierhttp://hdl.handle.net/10722/162343
ISSN
2015 Impact Factor: 3.324
2015 SCImago Journal Rankings: 1.823
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorHu, Ken_US
dc.contributor.authorLi, GRen_US
dc.contributor.authorNattel, Sen_US
dc.date.accessioned2012-09-05T05:19:08Z-
dc.date.available2012-09-05T05:19:08Z-
dc.date.issued1999en_US
dc.identifier.citationAmerican Journal Of Physiology - Heart And Circulatory Physiology, 1999, v. 276 n. 2 45-2, p. H488-H495en_US
dc.identifier.issn0363-6135en_US
dc.identifier.urihttp://hdl.handle.net/10722/162343-
dc.description.abstractBoth protein kinase C (PKC) and adenosine receptor activation have been shown to enhance ATP-sensitive K + (K(ATP)) channels. The present studies were designed to determine whether PKC mediates adenosine effects on the K(ATP) channel. The dependence of K(ATP) channel activity (nP(o)) on intracellular ATP concentration ([ATP](i)) was determined in excised rabbit ventricular membrane patches. External adenosine (100 μM in the pipette solution) significantly increased K(ATP) nP(o) at all [ATP](i) between 5 and 50 μM by decreasing channel sensitivity to [ATP](i) (dissociation constant increased from 7.4 ± 0.8 to 22.2 ± 3.1 μM, P < 0.001), an effect blocked by the adenosine receptor antagonist 8-phenyltheophylline (10 μM). When the highly selective PKC blocker bisindolylmaleimide (BIM) was included in the internal (bath) solution, the K(ATP)-stimulating action of adenosine was prevented. The addition of BIM to the superfusate rapidly inhibited K(ATP) channels activated by adenosine. Endogenous PKC activation by phorbol 12,13- didecanoate (PDD), but not administration of the inactive congener 4α-PDD, enhanced K(ATP) activity. Internal guanosine 5'-O-(2-thiodiphosphate) prevented K(ATP) activation by adenosine, an effect which could be overridden by exposure to PDD. We conclude that PKC mediates adenosine activation of K(ATP) channels in excised membrane patches in a membrane-delimited fashion.en_US
dc.languageengen_US
dc.publisherAmerican Physiological Society. The Journal's web site is located at http://intl-ajpheart.physiology.org/en_US
dc.relation.ispartofAmerican Journal of Physiology - Heart and Circulatory Physiologyen_US
dc.subject.meshAdenosine - Pharmacologyen_US
dc.subject.meshAdenosine Triphosphate - Pharmacologyen_US
dc.subject.meshAnimalsen_US
dc.subject.meshCell Membrane - Metabolismen_US
dc.subject.meshEnzyme Inhibitors - Pharmacologyen_US
dc.subject.meshGtp-Binding Proteins - Physiologyen_US
dc.subject.meshIndoles - Pharmacologyen_US
dc.subject.meshMaleimides - Pharmacologyen_US
dc.subject.meshMyocardium - Cytology - Metabolismen_US
dc.subject.meshPhorbol Esters - Pharmacologyen_US
dc.subject.meshPotassium Channels - Drug Effects - Physiologyen_US
dc.subject.meshProtein Kinase C - Physiologyen_US
dc.subject.meshRabbitsen_US
dc.subject.meshReceptors, Purinergic P1 - Physiologyen_US
dc.titleAdenosine-induced activation of ATP-sensitive K + channels in excised membrane patches is mediated by PKCen_US
dc.typeArticleen_US
dc.identifier.emailLi, GR:grli@hkucc.hku.hken_US
dc.identifier.authorityLi, GR=rp00476en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.pmid9950849-
dc.identifier.scopuseid_2-s2.0-0033058569en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0033058569&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume276en_US
dc.identifier.issue2 45-2en_US
dc.identifier.spageH488en_US
dc.identifier.epageH495en_US
dc.identifier.isiWOS:000078427100018-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridHu, K=7203085175en_US
dc.identifier.scopusauthoridLi, GR=7408462932en_US
dc.identifier.scopusauthoridNattel, S=36947837400en_US

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