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Article: Antisense oligodeoxynucleotides directed against Kv1.5 mRNA specifically inhibit ultrarapid delayed rectifier K+ current in cultured adult human atrial myocytes

TitleAntisense oligodeoxynucleotides directed against Kv1.5 mRNA specifically inhibit ultrarapid delayed rectifier K+ current in cultured adult human atrial myocytes
Authors
Issue Date1997
PublisherLippincott Williams & Wilkins. The Journal's web site is located at http://circres.ahajournals.org
Citation
Circulation Research, 1997, v. 80 n. 4, p. 572-579 How to Cite?
AbstractSeveral cloned K+ channel subunits are candidates to underlie macroscopic currents in the human heart, but direct evidence bearing on their role is lacking. The Kv1.5 K+ channel subunit has been suggested to play a potential role in human cardiac ultrarapid delayed rectifier (I(Kur)) and transient outward (I(to)) currents. To evaluate the role of proteins encoded by the Kv1.5 gene, we incubated cultured human atrial myocytes for 48 hours in medium containing antisense phosphorothioate oligodeoxynucleotides directed against octodecameric segments of the Kv1.5 mRNA coding sequence, the same concentration of homologous oligodeoxynucleotides with four mismatch mutations, or vehicle (control group). Cells exposed to antisense showed a highly significant (≃50%) reduction in I(Kur), whether measured by step current at the end of a 400-millisecond depolarizing pulse, tail current at - 20 mV, or current sensitive to a concentration of 4-aminopyridine (50 μmol/L) that is highly selective for I(Kur)-compared with control cells or cells exposed to mismatch oligodeoxynucleotides. In contrast, I(to) was not different among the three experimental groups. When cultured human ventricular myocytes were exposed to Kv1.5 antisense oligodeoxynucleotides with the same controls, no changes occurred in either I(to) or the sustained current at the end of a depolarizing pulse. We conclude that Kv1.5 channel subunits are essential to the expression of I(Kur) and do not play a role in I(to) in cultured human atrial myocytes. These studies provide the first direct evidence with an antisense approach for the equivalence between a macroscopic cardiac K+ current and a cloned K+ channel subunit and offer insights into the molecular electrophysiology of the human heart.
Persistent Identifierhttp://hdl.handle.net/10722/162198
ISSN
2015 Impact Factor: 11.551
2015 SCImago Journal Rankings: 5.755
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorFeng, Jen_US
dc.contributor.authorWible, Ben_US
dc.contributor.authorLi, GRen_US
dc.contributor.authorWang, Zen_US
dc.contributor.authorNattel, Sen_US
dc.date.accessioned2012-09-05T05:18:02Z-
dc.date.available2012-09-05T05:18:02Z-
dc.date.issued1997en_US
dc.identifier.citationCirculation Research, 1997, v. 80 n. 4, p. 572-579en_US
dc.identifier.issn0009-7330en_US
dc.identifier.urihttp://hdl.handle.net/10722/162198-
dc.description.abstractSeveral cloned K+ channel subunits are candidates to underlie macroscopic currents in the human heart, but direct evidence bearing on their role is lacking. The Kv1.5 K+ channel subunit has been suggested to play a potential role in human cardiac ultrarapid delayed rectifier (I(Kur)) and transient outward (I(to)) currents. To evaluate the role of proteins encoded by the Kv1.5 gene, we incubated cultured human atrial myocytes for 48 hours in medium containing antisense phosphorothioate oligodeoxynucleotides directed against octodecameric segments of the Kv1.5 mRNA coding sequence, the same concentration of homologous oligodeoxynucleotides with four mismatch mutations, or vehicle (control group). Cells exposed to antisense showed a highly significant (≃50%) reduction in I(Kur), whether measured by step current at the end of a 400-millisecond depolarizing pulse, tail current at - 20 mV, or current sensitive to a concentration of 4-aminopyridine (50 μmol/L) that is highly selective for I(Kur)-compared with control cells or cells exposed to mismatch oligodeoxynucleotides. In contrast, I(to) was not different among the three experimental groups. When cultured human ventricular myocytes were exposed to Kv1.5 antisense oligodeoxynucleotides with the same controls, no changes occurred in either I(to) or the sustained current at the end of a depolarizing pulse. We conclude that Kv1.5 channel subunits are essential to the expression of I(Kur) and do not play a role in I(to) in cultured human atrial myocytes. These studies provide the first direct evidence with an antisense approach for the equivalence between a macroscopic cardiac K+ current and a cloned K+ channel subunit and offer insights into the molecular electrophysiology of the human heart.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.meshAdulten_US
dc.subject.meshAgeden_US
dc.subject.meshCell Sizeen_US
dc.subject.meshCells, Cultureden_US
dc.subject.meshDelayed Rectifier Potassium Channelsen_US
dc.subject.meshHeart Atria - Drug Effects - Metabolismen_US
dc.subject.meshHeart Ventricles - Drug Effectsen_US
dc.subject.meshHumansen_US
dc.subject.meshMiddle Ageden_US
dc.subject.meshMuscle Fibers, Skeletal - Drug Effects - Metabolismen_US
dc.subject.meshOligonucleotides, Antisense - Pharmacologyen_US
dc.subject.meshPatch-Clamp Techniquesen_US
dc.subject.meshPotassium Channels - Drug Effects - Metabolismen_US
dc.subject.meshPotassium Channels, Voltage-Gateden_US
dc.subject.meshVentricular Functionen_US
dc.titleAntisense oligodeoxynucleotides directed against Kv1.5 mRNA specifically inhibit ultrarapid delayed rectifier K+ current in cultured adult 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.pmid9118489-
dc.identifier.scopuseid_2-s2.0-0031003283en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0031003283&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume80en_US
dc.identifier.issue4en_US
dc.identifier.spage572en_US
dc.identifier.epage579en_US
dc.identifier.isiWOS:A1997WQ09300017-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridFeng, J=7403884361en_US
dc.identifier.scopusauthoridWible, B=7003574312en_US
dc.identifier.scopusauthoridLi, GR=7408462932en_US
dc.identifier.scopusauthoridWang, Z=7410039597en_US
dc.identifier.scopusauthoridNattel, S=36048738800en_US

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