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Article: Current in Human and Rabbit Ventricular Myocytes

TitleCurrent in Human and Rabbit Ventricular Myocytes
Authors
Issue Date1996
PublisherLippincott Williams & Wilkins. The Journal's web site is located at http://circres.ahajournals.org
Citation
Circulation Research, 1996, v. 78 n. 3, p. 492-498 How to Cite?
AbstractMediators involved in ischemic preconditioning, such as adenosine and norepinephrine, can activate protein kinase C (PKC), and a variety of observations suggest that both PKC and ATP-sensitive K+ current (IKATP) play essential roles in ischemic preconditioning. PKC is therefore a candidate to link receptor binding to IKATP activation, but it has not been shown whether and how PKC can activate IKATP in the heart. The present study was designed to determine whether PKC can activate IKATP in rabbit and human ventricular myocytes. Under conditions designed to minimize Na+ and Ca2+ currents, dialysis of rabbit ventricular myocytes with pipette solutions containing reduced [ATP] elicited IKATP, with a 50% effective concentration (EC50) of 260 μmol/L. In cells that failed to show IKATP under control conditions, superfusion with 1 μmol/L phorbol 12,13-didecanoate (PDD) elicited IKATP in a fashion that depended on pipette [ATP], with an [ATP] EC50 of 601 μmol/L. PDD-induced IKATP activation was concentration dependent, with an EC50 of 7.1 nmol/L. The highly selective PKC inhibitor bisindolylmaleimide totally prevented IKATP activation by PDD, and in blinded experiments, 1 μmol/L PDD elicited IKATP in eight of nine cells, whereas its non-PKC-stimulating analogue 4α-PDD failed to elicit IKATP in any of the five cells tested (P=.003). Similar experiments were conducted in human ventricular myocytes and showed that 0.1 μmol/L PDD elicited IKATP at pipette [ATP] of 100 and 400 μmol/L (five of five cells at each concentration) but not at 1 mmol/L [ATP] (none of five cells). We conclude that PKC activates IKATP in rabbit and human ventricular myocytes by reducing channel sensitivity to intracellular ATP. This finding has potentially important implications for understanding the mechanisms of ischemic preconditioning.
Persistent Identifierhttp://hdl.handle.net/10722/162159
ISSN
2015 Impact Factor: 11.551
2015 SCImago Journal Rankings: 5.755
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorHu, Ken_US
dc.contributor.authorDuan, Den_US
dc.contributor.authorLi, GRen_US
dc.contributor.authorNattel, Sen_US
dc.date.accessioned2012-09-05T05:17:43Z-
dc.date.available2012-09-05T05:17:43Z-
dc.date.issued1996en_US
dc.identifier.citationCirculation Research, 1996, v. 78 n. 3, p. 492-498en_US
dc.identifier.issn0009-7330en_US
dc.identifier.urihttp://hdl.handle.net/10722/162159-
dc.description.abstractMediators involved in ischemic preconditioning, such as adenosine and norepinephrine, can activate protein kinase C (PKC), and a variety of observations suggest that both PKC and ATP-sensitive K+ current (IKATP) play essential roles in ischemic preconditioning. PKC is therefore a candidate to link receptor binding to IKATP activation, but it has not been shown whether and how PKC can activate IKATP in the heart. The present study was designed to determine whether PKC can activate IKATP in rabbit and human ventricular myocytes. Under conditions designed to minimize Na+ and Ca2+ currents, dialysis of rabbit ventricular myocytes with pipette solutions containing reduced [ATP] elicited IKATP, with a 50% effective concentration (EC50) of 260 μmol/L. In cells that failed to show IKATP under control conditions, superfusion with 1 μmol/L phorbol 12,13-didecanoate (PDD) elicited IKATP in a fashion that depended on pipette [ATP], with an [ATP] EC50 of 601 μmol/L. PDD-induced IKATP activation was concentration dependent, with an EC50 of 7.1 nmol/L. The highly selective PKC inhibitor bisindolylmaleimide totally prevented IKATP activation by PDD, and in blinded experiments, 1 μmol/L PDD elicited IKATP in eight of nine cells, whereas its non-PKC-stimulating analogue 4α-PDD failed to elicit IKATP in any of the five cells tested (P=.003). Similar experiments were conducted in human ventricular myocytes and showed that 0.1 μmol/L PDD elicited IKATP at pipette [ATP] of 100 and 400 μmol/L (five of five cells at each concentration) but not at 1 mmol/L [ATP] (none of five cells). We conclude that PKC activates IKATP in rabbit and human ventricular myocytes by reducing channel sensitivity to intracellular ATP. This finding has potentially important implications for understanding the mechanisms of ischemic preconditioning.en_US
dc.languageengen_US
dc.publisherLippincott Williams & Wilkins. The Journal's web site is located at http://circres.ahajournals.orgen_US
dc.relation.ispartofCirculation Researchen_US
dc.subject.meshAdenosine Triphosphate - Pharmacologyen_US
dc.subject.meshAnimalsen_US
dc.subject.meshCells, Cultureden_US
dc.subject.meshDose-Response Relationship, Drugen_US
dc.subject.meshEnzyme Activationen_US
dc.subject.meshHeart Ventricles - Cytology - Enzymology - Metabolismen_US
dc.subject.meshHumansen_US
dc.subject.meshMyocardial Ischemia - Enzymology - Metabolismen_US
dc.subject.meshPotassium Channels - Drug Effects - Metabolismen_US
dc.subject.meshProtein Kinase C - Metabolismen_US
dc.subject.meshRabbitsen_US
dc.titleCurrent in Human and Rabbit Ventricular Myocytesen_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.pmid8593708en_US
dc.identifier.scopuseid_2-s2.0-0030050099en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0030050099&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume78en_US
dc.identifier.issue3en_US
dc.identifier.spage492en_US
dc.identifier.epage498en_US
dc.identifier.isiWOS:A1996TX27200017-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridHu, K=7203085175en_US
dc.identifier.scopusauthoridDuan, D=7007026256en_US
dc.identifier.scopusauthoridLi, GR=7408462932en_US
dc.identifier.scopusauthoridNattel, S=36048738800en_US

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