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Article: Calcium-activated transient outward chloride current and phase 1 repolarization of swine ventricular action potential

TitleCalcium-activated transient outward chloride current and phase 1 repolarization of swine ventricular action potential
Authors
Issue Date2003
PublisherOxford University Press. The Journal's web site is located at http://cardiovascres.oxfordjournals.org
Citation
Cardiovascular Research, 2003, v. 58 n. 1, p. 89-98 How to Cite?
AbstractObjective: It is unknown whether 4-aminopyridine- (4-AP-) sensitive transient outward K+ current (Ito1) and/or Ca2+-activated transient outward Cl- current (ICa.Cl or Ito2) contribute(s) to phase 1 repolarization of pig ventricular action potential (AP). The purpose of the present study was to determine ionic contribution of the phase 1 repolarization of AP in pig ventricle. Methods: We used whole-cell patch techniques to record APs and membrane currents, and Western immunoblotting analysis to detect expression of Ito1 protein (Kv4.2 or Kv4.3) in pig ventricular myocytes. Results: A transient outward current (Ito) was activated upon depolarization voltage steps to between -10 and +60 mV from -50 mV in pig ventricular cells, and the Ito was resistant to 4-AP application, but sensitive to the inhibition by ryanodine (10 μmol/l) and the Ca2+ channel blockade, and the Cl- channel blocker 4,4′-diisothiocyanostilben-2,2′disulfonic acid (DIDS, 150 μmol/l). The current was diminished by external Cl- (Clo -) replacement and showed a 'bell-shaped' I-V relationship at room temperature, typical of Ito2. No difference in Ito2 was observed in the regional cells from epicardium, midmyocardium, and endocardium of left ventricle. APs showed significant phase 1 and 'spike and dome' in pig ventricular myocytes. The phase 1 and 'spike and dome' of APs were not affected by 4-AP (3 mmol/l), but abolished by replacing Clo - and by application of 100 μmol/l DIDS, suggesting Ito2 contribution. Western immunoblotting analysis showed no evidence for the expression of 4-AP-sensitive Ito1 channel protein (Kv4.2 or Kv4.3) in pig ventricular cells. Conclusion: The results indicate that 4-AP-sensitive Ito1 is not expressed, and only Ca2+-activated Ito2 is present in pig cardiac cells, which contributes importantly to the phase 1 repolarization of ventricular APs in this species. © 2003 European Society of Cardiology. Published by Elsevier Science B.V. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/77375
ISSN
2015 Impact Factor: 5.465
2015 SCImago Journal Rankings: 2.897
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLi, GRen_HK
dc.contributor.authorDu, XLen_HK
dc.contributor.authorSiow, YLen_HK
dc.contributor.authorKarmin, Oen_HK
dc.contributor.authorTse, HFen_HK
dc.contributor.authorLau, CPen_HK
dc.date.accessioned2010-09-06T07:31:13Z-
dc.date.available2010-09-06T07:31:13Z-
dc.date.issued2003en_HK
dc.identifier.citationCardiovascular Research, 2003, v. 58 n. 1, p. 89-98en_HK
dc.identifier.issn0008-6363en_HK
dc.identifier.urihttp://hdl.handle.net/10722/77375-
dc.description.abstractObjective: It is unknown whether 4-aminopyridine- (4-AP-) sensitive transient outward K+ current (Ito1) and/or Ca2+-activated transient outward Cl- current (ICa.Cl or Ito2) contribute(s) to phase 1 repolarization of pig ventricular action potential (AP). The purpose of the present study was to determine ionic contribution of the phase 1 repolarization of AP in pig ventricle. Methods: We used whole-cell patch techniques to record APs and membrane currents, and Western immunoblotting analysis to detect expression of Ito1 protein (Kv4.2 or Kv4.3) in pig ventricular myocytes. Results: A transient outward current (Ito) was activated upon depolarization voltage steps to between -10 and +60 mV from -50 mV in pig ventricular cells, and the Ito was resistant to 4-AP application, but sensitive to the inhibition by ryanodine (10 μmol/l) and the Ca2+ channel blockade, and the Cl- channel blocker 4,4′-diisothiocyanostilben-2,2′disulfonic acid (DIDS, 150 μmol/l). The current was diminished by external Cl- (Clo -) replacement and showed a 'bell-shaped' I-V relationship at room temperature, typical of Ito2. No difference in Ito2 was observed in the regional cells from epicardium, midmyocardium, and endocardium of left ventricle. APs showed significant phase 1 and 'spike and dome' in pig ventricular myocytes. The phase 1 and 'spike and dome' of APs were not affected by 4-AP (3 mmol/l), but abolished by replacing Clo - and by application of 100 μmol/l DIDS, suggesting Ito2 contribution. Western immunoblotting analysis showed no evidence for the expression of 4-AP-sensitive Ito1 channel protein (Kv4.2 or Kv4.3) in pig ventricular cells. Conclusion: The results indicate that 4-AP-sensitive Ito1 is not expressed, and only Ca2+-activated Ito2 is present in pig cardiac cells, which contributes importantly to the phase 1 repolarization of ventricular APs in this species. © 2003 European Society of Cardiology. Published by Elsevier Science B.V. All rights reserved.en_HK
dc.languageengen_HK
dc.publisherOxford University Press. The Journal's web site is located at http://cardiovascres.oxfordjournals.orgen_HK
dc.relation.ispartofCardiovascular Researchen_HK
dc.rightsCardiovascular Research. Copyright © Elsevier BV.en_HK
dc.subject.mesh4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid - pharmacologyen_HK
dc.subject.mesh4-Aminopyridine - pharmacologyen_HK
dc.subject.meshAction Potentials - drug effects - physiologyen_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshBlotting, Western - methodsen_HK
dc.subject.meshCadmium - pharmacologyen_HK
dc.subject.meshCalcium - metabolismen_HK
dc.subject.meshCalcium Channel Blockers - pharmacologyen_HK
dc.subject.meshChloride Channels - drug effects - metabolismen_HK
dc.subject.meshHeart Ventriclesen_HK
dc.subject.meshMyocytes, Cardiac - drug effects - metabolismen_HK
dc.subject.meshPatch-Clamp Techniquesen_HK
dc.subject.meshPotassium Channel Blockers - pharmacologyen_HK
dc.subject.meshPotassium Channels - analysis - metabolismen_HK
dc.subject.meshPotassium Channels, Voltage-Gateden_HK
dc.subject.meshRyanodine - pharmacologyen_HK
dc.subject.meshShal Potassium Channelsen_HK
dc.subject.meshSwineen_HK
dc.titleCalcium-activated transient outward chloride current and phase 1 repolarization of swine ventricular action potentialen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0008-6363&volume=58 &issue=1&spage=89&epage=98&date=2003&atitle=Calcium-activated+Transient+Outward+Chloride+Current+and+Phase+1+Repolarization+of+Swine+Ventricular+Action+Potentialen_HK
dc.identifier.emailLi, GR:grli@hkucc.hku.hken_HK
dc.identifier.emailTse, HF:hftse@hkucc.hku.hken_HK
dc.identifier.authorityLi, GR=rp00476en_HK
dc.identifier.authorityTse, HF=rp00428en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/S0008-6363(02)00859-3en_HK
dc.identifier.pmid12667949-
dc.identifier.scopuseid_2-s2.0-0037401278en_HK
dc.identifier.hkuros81650en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0037401278&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume58en_HK
dc.identifier.issue1en_HK
dc.identifier.spage89en_HK
dc.identifier.epage98en_HK
dc.identifier.isiWOS:000182446700009-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridLi, GR=7408462932en_HK
dc.identifier.scopusauthoridDu, XL=9036718000en_HK
dc.identifier.scopusauthoridSiow, YL=7003336463en_HK
dc.identifier.scopusauthoridKarmin, O=6604083266en_HK
dc.identifier.scopusauthoridTse, HF=7006070805en_HK
dc.identifier.scopusauthoridLau, CP=7401968501en_HK

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