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Article: Evidence for two components of delayed rectifier K + current in human ventricular myocytes

TitleEvidence for two components of delayed rectifier K + current in human 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. 4, p. 689-696 How to Cite?
AbstractPrevious voltage-clamp studies have suggested that the delayed rectifier current (I(K)) is small or absent in the human ventricle and, when present, consists only of the rapid component (I(Kr)); however, molecular studies suggest the presence of functionally important I(K) in the human heart, specific I(Kr) blockers are known to delay ventricular repolarization and cause the long QT syndrome in humans, and we have shown that the expression of I(K) is strongly influenced by cell isolation techniques. The present experiments were designed to assess the expression of I(K) in myocytes obtained by arterial perfusion of right ventricular tissue from explanted human hearts. Of 35 cells from three hearts, 33 (94%) showed time-dependent currents typical of I(K). The envelope-of-tails test was not satisfied under control conditions but became satisfied in the presence of the benzenesulfonamide E-4031 (5 μmol/L). E-4031 suppressed a portion of I(K) in 32 of 33 cells, with properties of the drug-sensitive and -resistant components consistent with previous descriptions of I(Kr) and the slow component (I(Kr), respectively. Action potential duration to 95% repolarization at 1 Hz was prolonged by E-4031 from 336±16 (mean±SEM) to 421±19 ms (n=5, P<.01), indicating a functional role for I(K). Indapamide, a diuretic agent previously shown to inhibit I(Ks) selectively, suppressed E- 4031-resistant current. The presence of a third type of delayed rectifier, the ultrarapid delayed rectifier current (I(Kur)), was evaluated with the use of depolarizing prepulses and low concentrations (50 μmol/L) of 4- aminopyridine. Although these techniques revealed clear I(Kur) in five of five human atrial cells, no corresponding component was observed in any of five human ventricular myocytes. We conclude that a functionally significant I(Kr) with components corresponding to I(Kr) and I(Ks), is present in human ventricular cells, whereas I(Kur) appears to be absent. These findings are important for understanding the molecular, physiological, and pharmacological determinants of human ventricular repolarization and arrhythmias.
Persistent Identifierhttp://hdl.handle.net/10722/162154
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.authorYue, Len_US
dc.contributor.authorCarrier, Men_US
dc.contributor.authorNattel, Sen_US
dc.date.accessioned2012-09-05T05:17:41Z-
dc.date.available2012-09-05T05:17:41Z-
dc.date.issued1996en_US
dc.identifier.citationCirculation Research, 1996, v. 78 n. 4, p. 689-696en_US
dc.identifier.issn0009-7330en_US
dc.identifier.urihttp://hdl.handle.net/10722/162154-
dc.description.abstractPrevious voltage-clamp studies have suggested that the delayed rectifier current (I(K)) is small or absent in the human ventricle and, when present, consists only of the rapid component (I(Kr)); however, molecular studies suggest the presence of functionally important I(K) in the human heart, specific I(Kr) blockers are known to delay ventricular repolarization and cause the long QT syndrome in humans, and we have shown that the expression of I(K) is strongly influenced by cell isolation techniques. The present experiments were designed to assess the expression of I(K) in myocytes obtained by arterial perfusion of right ventricular tissue from explanted human hearts. Of 35 cells from three hearts, 33 (94%) showed time-dependent currents typical of I(K). The envelope-of-tails test was not satisfied under control conditions but became satisfied in the presence of the benzenesulfonamide E-4031 (5 μmol/L). E-4031 suppressed a portion of I(K) in 32 of 33 cells, with properties of the drug-sensitive and -resistant components consistent with previous descriptions of I(Kr) and the slow component (I(Kr), respectively. Action potential duration to 95% repolarization at 1 Hz was prolonged by E-4031 from 336±16 (mean±SEM) to 421±19 ms (n=5, P<.01), indicating a functional role for I(K). Indapamide, a diuretic agent previously shown to inhibit I(Ks) selectively, suppressed E- 4031-resistant current. The presence of a third type of delayed rectifier, the ultrarapid delayed rectifier current (I(Kur)), was evaluated with the use of depolarizing prepulses and low concentrations (50 μmol/L) of 4- aminopyridine. Although these techniques revealed clear I(Kur) in five of five human atrial cells, no corresponding component was observed in any of five human ventricular myocytes. We conclude that a functionally significant I(Kr) with components corresponding to I(Kr) and I(Ks), is present in human ventricular cells, whereas I(Kur) appears to be absent. These findings are important for understanding the molecular, physiological, and pharmacological determinants of human ventricular 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.mesh4-Aminopyridine - Pharmacologyen_US
dc.subject.meshAction Potentials - Drug Effectsen_US
dc.subject.meshAdulten_US
dc.subject.meshAnti-Arrhythmia Agents - Pharmacologyen_US
dc.subject.meshDiuretics - Pharmacologyen_US
dc.subject.meshElectric Conductivityen_US
dc.subject.meshHeart Ventricles - Cytologyen_US
dc.subject.meshHumansen_US
dc.subject.meshIndapamide - Pharmacologyen_US
dc.subject.meshMiddle Ageden_US
dc.subject.meshMyocardium - Cytologyen_US
dc.subject.meshPiperidines - Pharmacologyen_US
dc.subject.meshPotassium - Antagonists & Inhibitors - Physiologyen_US
dc.subject.meshPotassium Channels - Drug Effects - Physiologyen_US
dc.subject.meshPyridines - Pharmacologyen_US
dc.subject.meshReaction Timeen_US
dc.subject.meshVentricular Function - Drug Effectsen_US
dc.titleEvidence for two components of delayed rectifier K + current in human 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.pmid8635226-
dc.identifier.scopuseid_2-s2.0-0029997391en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0029997391&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume78en_US
dc.identifier.issue4en_US
dc.identifier.spage689en_US
dc.identifier.epage696en_US
dc.identifier.isiWOS:A1996UC17600020-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridLi, GR=7408462932en_US
dc.identifier.scopusauthoridFeng, J=7403884361en_US
dc.identifier.scopusauthoridYue, L=7101974873en_US
dc.identifier.scopusauthoridCarrier, M=7101604979en_US
dc.identifier.scopusauthoridNattel, S=36048738800en_US

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