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Conference Paper: Ionic mechanisms of chloroform induced arrhythmia

TitleIonic mechanisms of chloroform induced arrhythmia
Authors
KeywordsBiology
Biochemistry
Issue Date2009
PublisherWiley-Blackwell Publishing Ltd.. The Journal's web site is located at http://www.febsjournal.org/
Citation
The 34th FEBS Congress, Prague, Czech Republic, 4-9 July 2009. In The FEBS Journal, 2009, v. 276 suppl. 1, p. 354-355, abstract P8-193 How to Cite?
AbstractChloroform, an organic solvent widely used in industrial production, is found to cause intoxication of lethal arrhythmias. However, the ionic mechanisms of its arrhythmogenic effects are still unknown. The present study was designed to investigate the electrophysiological basis involved. METHODS: In isolated rat heat model, ECGs were recorded and analyzed to investigate the arrhythmogenic effects of chloroform. Whole-cell patch clamp was employed to study its effects on pacemaker channel (HCN2), Nav1.5 channel, human cardiac ether-a-go-go related (hERG) K+ channel or inward rectifier K+ channel (Kir2.1), which were stably expressed in HEK 239 cells respectively. RESULTS: In Langendoff-perfused rat hearts, ECG recording showed that chloroform (5 mM) slowed the heart rate. In addition, chloroform inhibited HCN2, Nav1.5 and hERG channels in a concentration-dependent manner; however, it had no effect on Kir2.1 channel. Specifically, chloroform inhibited HCN2 channel with IC50 at 3.4 mM. In addition, it shifted the activation curve of HCN2 channel toward hyperpolarized potential. Similarly, chloroform suppressed Nav1.5 currents to 75.5%, 52.4%, and 17.2% of basal levels at 5, 10 and 15 mM, respectively. Furthermore, it slowed down the recovery of Nav1.5 channel from inactivation, and it shifted the inactivation curve toward hyperpolarized potential, leaving no difference on the activation curve. For hERG channel, chloroform inhibited it with IC50 at 4.3 mM. CONCLUSION: These results demonstrate that chloroform blocks multiple cardiac ion channels including HCN2 channel, Nav1.5 channel and hERG channels, which might contribute to the chloroform- induced lethal arrhythmias. These findings provide potential targets for effective treatments of acute chloroform intoxication.
DescriptionThis journal suppl. entitled: Special Issue: Abstracts of the 34th FEBS Congress
Poster Presentations - P8 From Biochemistry to Medicine: abstract P8-193
Persistent Identifierhttp://hdl.handle.net/10722/102314
ISSN
2015 Impact Factor: 4.237
2015 SCImago Journal Rankings: 2.141

 

DC FieldValueLanguage
dc.contributor.authorZhou, Yen_HK
dc.contributor.authorWong, TMen_HK
dc.contributor.authorLi, GRen_HK
dc.date.accessioned2010-09-25T20:25:39Z-
dc.date.available2010-09-25T20:25:39Z-
dc.date.issued2009en_HK
dc.identifier.citationThe 34th FEBS Congress, Prague, Czech Republic, 4-9 July 2009. In The FEBS Journal, 2009, v. 276 suppl. 1, p. 354-355, abstract P8-193en_HK
dc.identifier.issn1742-464Xen_HK
dc.identifier.urihttp://hdl.handle.net/10722/102314-
dc.descriptionThis journal suppl. entitled: Special Issue: Abstracts of the 34th FEBS Congress-
dc.descriptionPoster Presentations - P8 From Biochemistry to Medicine: abstract P8-193-
dc.description.abstractChloroform, an organic solvent widely used in industrial production, is found to cause intoxication of lethal arrhythmias. However, the ionic mechanisms of its arrhythmogenic effects are still unknown. The present study was designed to investigate the electrophysiological basis involved. METHODS: In isolated rat heat model, ECGs were recorded and analyzed to investigate the arrhythmogenic effects of chloroform. Whole-cell patch clamp was employed to study its effects on pacemaker channel (HCN2), Nav1.5 channel, human cardiac ether-a-go-go related (hERG) K+ channel or inward rectifier K+ channel (Kir2.1), which were stably expressed in HEK 239 cells respectively. RESULTS: In Langendoff-perfused rat hearts, ECG recording showed that chloroform (5 mM) slowed the heart rate. In addition, chloroform inhibited HCN2, Nav1.5 and hERG channels in a concentration-dependent manner; however, it had no effect on Kir2.1 channel. Specifically, chloroform inhibited HCN2 channel with IC50 at 3.4 mM. In addition, it shifted the activation curve of HCN2 channel toward hyperpolarized potential. Similarly, chloroform suppressed Nav1.5 currents to 75.5%, 52.4%, and 17.2% of basal levels at 5, 10 and 15 mM, respectively. Furthermore, it slowed down the recovery of Nav1.5 channel from inactivation, and it shifted the inactivation curve toward hyperpolarized potential, leaving no difference on the activation curve. For hERG channel, chloroform inhibited it with IC50 at 4.3 mM. CONCLUSION: These results demonstrate that chloroform blocks multiple cardiac ion channels including HCN2 channel, Nav1.5 channel and hERG channels, which might contribute to the chloroform- induced lethal arrhythmias. These findings provide potential targets for effective treatments of acute chloroform intoxication.-
dc.languageengen_HK
dc.publisherWiley-Blackwell Publishing Ltd.. The Journal's web site is located at http://www.febsjournal.org/en_HK
dc.relation.ispartofThe FEBS Journalen_HK
dc.rightsThe definitive version is available at www3.interscience.wiley.comen_HK
dc.subjectBiology-
dc.subjectBiochemistry-
dc.titleIonic mechanisms of chloroform induced arrhythmiaen_HK
dc.typeConference_Paperen_HK
dc.identifier.emailWong, TM: tm.wong@hkuspace.hku.hken_HK
dc.identifier.emailLi, GR: grli@hkucc.hku.hken_HK
dc.identifier.authorityLi, GR=rp00476en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1111/j.1742-4658.2009.07049.x-
dc.identifier.hkuros166412en_HK
dc.identifier.volume276en_HK
dc.identifier.issuesuppl. 1en_HK
dc.identifier.spage354en_HK
dc.identifier.epage355en_HK
dc.publisher.placeUnited Kingdom-

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