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Article: Adrenergic modulation of ultrarapid delayed rectifier K+ current in human atrial myocytes

TitleAdrenergic modulation of ultrarapid delayed rectifier K+ current in human atrial 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. 5, p. 903-915 How to Cite?
AbstractThe ultrarapid delayed rectifier K+ current (I(kur)) in human atrial cells appears to correspond to Kv1.5 cloned channels and to play an important role in human atrial repolarization. Kv1.5 channels have consensus sites for phosphorylation, by proteins kinase A and C, suggesting possible modulation by adrenergic stimulation. The present study was designed to assess the adrenergic regulation of I(km) in human atrial myocytes. Isoproterenol increased I(km) in human atrial myocytes. Isoproterenol increased dependent manner, with significant effects at concentrations as low as 10 nmol/L. The effects of isoproterenol were reversible by washout or by the addition of propranolol (1 μmol/L). Isoproterenol's effects were mimicked by the direct adenylate cyclase stimulator, forskolin, and by the membrane-permeable form of cAMP, 8-bromo cAMP. Isoproterenol had no effect on 1 (kur) when the protein kinase A inhibit peptide, PKI(6-22) amide, was included in the pipette solution; in a separate set of experiments in which isoproterenol alone increased I(kur) by 45 ± 9% relative to control, subsequent superfusion with isoproterenol in the presence of the protein kinase inhibitor H-7 failed to alter I(kur). In contrast to isoproterenol, phenylephrine (in the presence of propranolol to block β-adrenergic effects induced a concentration-dependent inhibition of I(kur), with significant effects observed at concentrations as low as 10 μmol/L/. The inhibitory actions of phenylephrine were reversed by the addition of prazosin and prevented by coadministration with a highly selective inhibitor of protein kinase C, bisindolylmaleimide. These results indicate that β adrenergic stimulation enhances, whereas α-adrenergic stimulation inhibits, I(kur) and suggest that these actions are mediated by protein kinase A and protein kinase C, respectively. The modulation of I(km) by adrenergic influences is a potentially novel control mechanism for human atrial repolarization and arrhythmias.
Persistent Identifierhttp://hdl.handle.net/10722/162134
ISSN
2015 Impact Factor: 11.551
2015 SCImago Journal Rankings: 5.755
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLi, GRen_US
dc.contributor.authorFeng, Jen_US
dc.contributor.authorWang, Zen_US
dc.contributor.authorFermini, Ben_US
dc.contributor.authorNattel, Sen_US
dc.date.accessioned2012-09-05T05:17:33Z-
dc.date.available2012-09-05T05:17:33Z-
dc.date.issued1996en_US
dc.identifier.citationCirculation Research, 1996, v. 78 n. 5, p. 903-915en_US
dc.identifier.issn0009-7330en_US
dc.identifier.urihttp://hdl.handle.net/10722/162134-
dc.description.abstractThe ultrarapid delayed rectifier K+ current (I(kur)) in human atrial cells appears to correspond to Kv1.5 cloned channels and to play an important role in human atrial repolarization. Kv1.5 channels have consensus sites for phosphorylation, by proteins kinase A and C, suggesting possible modulation by adrenergic stimulation. The present study was designed to assess the adrenergic regulation of I(km) in human atrial myocytes. Isoproterenol increased I(km) in human atrial myocytes. Isoproterenol increased dependent manner, with significant effects at concentrations as low as 10 nmol/L. The effects of isoproterenol were reversible by washout or by the addition of propranolol (1 μmol/L). Isoproterenol's effects were mimicked by the direct adenylate cyclase stimulator, forskolin, and by the membrane-permeable form of cAMP, 8-bromo cAMP. Isoproterenol had no effect on 1 (kur) when the protein kinase A inhibit peptide, PKI(6-22) amide, was included in the pipette solution; in a separate set of experiments in which isoproterenol alone increased I(kur) by 45 ± 9% relative to control, subsequent superfusion with isoproterenol in the presence of the protein kinase inhibitor H-7 failed to alter I(kur). In contrast to isoproterenol, phenylephrine (in the presence of propranolol to block β-adrenergic effects induced a concentration-dependent inhibition of I(kur), with significant effects observed at concentrations as low as 10 μmol/L/. The inhibitory actions of phenylephrine were reversed by the addition of prazosin and prevented by coadministration with a highly selective inhibitor of protein kinase C, bisindolylmaleimide. These results indicate that β adrenergic stimulation enhances, whereas α-adrenergic stimulation inhibits, I(kur) and suggest that these actions are mediated by protein kinase A and protein kinase C, respectively. The modulation of I(km) by adrenergic influences is a potentially novel control mechanism for human atrial repolarization and arrhythmias.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.mesh8-Bromo Cyclic Adenosine Monophosphate - Pharmacologyen_US
dc.subject.meshAtrial Function - Drug Effectsen_US
dc.subject.meshElectric Conductivityen_US
dc.subject.meshForskolin - Pharmacologyen_US
dc.subject.meshHeart Atria - Cytologyen_US
dc.subject.meshHumansen_US
dc.subject.meshIndoles - Pharmacologyen_US
dc.subject.meshIsoproterenol - Pharmacologyen_US
dc.subject.meshMaleimides - Pharmacologyen_US
dc.subject.meshMyocardium - Cytologyen_US
dc.subject.meshPhenylephrine - Pharmacologyen_US
dc.subject.meshPotassium Channels - Physiologyen_US
dc.subject.meshProtein Kinase C - Antagonists & Inhibitorsen_US
dc.subject.meshReceptors, Adrenergic - Physiologyen_US
dc.subject.meshTime Factorsen_US
dc.titleAdrenergic modulation of ultrarapid delayed rectifier K+ current in human atrial 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.pmid8620611-
dc.identifier.scopuseid_2-s2.0-0029876330en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0029876330&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume78en_US
dc.identifier.issue5en_US
dc.identifier.spage903en_US
dc.identifier.epage915en_US
dc.identifier.isiWOS:A1996UH45300019-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridLi, GR=7408462932en_US
dc.identifier.scopusauthoridFeng, J=7403884361en_US
dc.identifier.scopusauthoridWang, Z=7410039597en_US
dc.identifier.scopusauthoridFermini, B=6603996429en_US
dc.identifier.scopusauthoridNattel, S=36048738800en_US

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