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Conference Paper: Protein tyrosine kinases regulate human cardiac KV4.3 channel

TitleProtein tyrosine kinases regulate human cardiac KV4.3 channel
Authors
KeywordsCardiovascular disease
Issue Date2009
PublisherHong Kong College of Cardiology. The Journal's web site is located at http://www.hkcchk.com/journals.php#3
Citation
The 13th Annual Scientific Meeting of the Institute of Cardiovascular Science and Medicine (ICSM), Hong Kong, 12 December 2009. In Journal of the Hong Kong College of Cardiology, 2009, v. 17 n. 2, p. 58, abstract no. P10 How to Cite?
AbstractBACKGROUND: The transient outward K+ current Ito (encoded by Kv4.3) plays an important role in the phase 1 rapid repolarization of cardiac action potentials in the heart. Modulation of Ito by intracellular signal transduction is not understood. The present study was designed to determine whether hKv4.3 channel (α-subunit of human cardiac Ito) is regulated by protein tyrosine kinases (PTKs) in HEK 293 cells stably expressing human Kv4.3 gene using a whole-cell patch clamp technique. RESULTS: It was found that human cardiac Kv4.3 current amplitude was remarkably inhibited by the broad-spectrum PTK inhibitor genistein (10 μM), and the inhibition was partially antagonized by the protein tyrosine phosphoatases (PTPs) inhibitor orthovandate (1 mM). It is interesting that the selective EGFR (epidermal growth factor receptor) kinase inhibitor AG556 (10 μM) reversibly reduced Kv4.3 current, and the inhibitory effect was almost fully countered by orthovandate. In addition, the Src-family kinase inhibitor PP2 (10 μM) also decreased hKv4.3 current and the effect was partially antagonized by orthoavanadate. Immunoprecipitation and Western blot analysis revealed that tyrosine phosphorylation level of hKv4.3 channel was reduced by genistein, AG556 or PP2. Their reduction of hKv4.3 channel phosphorylation level was reversed by orthovanadate. CONCLUSION: These results demonstrate that hKv4.3 channel is regulated by both EGFR kinase and Src-family kinases. EGFR and Src-family kinases favor tyrosine phosphorlation of the channel, and therefore may affect the cardiac electrophysiology.
DescriptionPoster Presentation: abstract no. P10
Persistent Identifierhttp://hdl.handle.net/10722/129838
ISSN
2015 SCImago Journal Rankings: 0.102

 

DC FieldValueLanguage
dc.contributor.authorZhang, YHen_US
dc.contributor.authorLau, CPen_US
dc.contributor.authorTse, HFen_US
dc.contributor.authorLi, GRen_US
dc.date.accessioned2010-12-23T08:42:47Z-
dc.date.available2010-12-23T08:42:47Z-
dc.date.issued2009en_US
dc.identifier.citationThe 13th Annual Scientific Meeting of the Institute of Cardiovascular Science and Medicine (ICSM), Hong Kong, 12 December 2009. In Journal of the Hong Kong College of Cardiology, 2009, v. 17 n. 2, p. 58, abstract no. P10en_US
dc.identifier.issn1027-7811-
dc.identifier.urihttp://hdl.handle.net/10722/129838-
dc.descriptionPoster Presentation: abstract no. P10-
dc.description.abstractBACKGROUND: The transient outward K+ current Ito (encoded by Kv4.3) plays an important role in the phase 1 rapid repolarization of cardiac action potentials in the heart. Modulation of Ito by intracellular signal transduction is not understood. The present study was designed to determine whether hKv4.3 channel (α-subunit of human cardiac Ito) is regulated by protein tyrosine kinases (PTKs) in HEK 293 cells stably expressing human Kv4.3 gene using a whole-cell patch clamp technique. RESULTS: It was found that human cardiac Kv4.3 current amplitude was remarkably inhibited by the broad-spectrum PTK inhibitor genistein (10 μM), and the inhibition was partially antagonized by the protein tyrosine phosphoatases (PTPs) inhibitor orthovandate (1 mM). It is interesting that the selective EGFR (epidermal growth factor receptor) kinase inhibitor AG556 (10 μM) reversibly reduced Kv4.3 current, and the inhibitory effect was almost fully countered by orthovandate. In addition, the Src-family kinase inhibitor PP2 (10 μM) also decreased hKv4.3 current and the effect was partially antagonized by orthoavanadate. Immunoprecipitation and Western blot analysis revealed that tyrosine phosphorylation level of hKv4.3 channel was reduced by genistein, AG556 or PP2. Their reduction of hKv4.3 channel phosphorylation level was reversed by orthovanadate. CONCLUSION: These results demonstrate that hKv4.3 channel is regulated by both EGFR kinase and Src-family kinases. EGFR and Src-family kinases favor tyrosine phosphorlation of the channel, and therefore may affect the cardiac electrophysiology.-
dc.languageengen_US
dc.publisherHong Kong College of Cardiology. The Journal's web site is located at http://www.hkcchk.com/journals.php#3-
dc.relation.ispartofJournal of the Hong Kong College of Cardiologyen_US
dc.rightsOpen Access Journal-
dc.subjectCardiovascular disease-
dc.titleProtein tyrosine kinases regulate human cardiac KV4.3 channelen_US
dc.typeConference_Paperen_US
dc.identifier.emailLau, CP: cplau@hku.hken_US
dc.identifier.emailTse, HF: hftse@hku.hken_US
dc.identifier.emailLi, GR: grli@hkucc.hku.hken_US
dc.identifier.authorityTse, HF=rp00428en_US
dc.identifier.authorityLi, GR=rp00476en_US
dc.description.naturelink_to_OA_fulltext-
dc.identifier.hkuros177393en_US
dc.identifier.volume17en_US
dc.identifier.issue2en_US
dc.identifier.spage58en_US
dc.identifier.epage58-
dc.publisher.placeHong Kong-
dc.description.otherThe 13th Annual Scientific Meeting of the Institute of Cardiovascular Science and Medicine (ICSM), Hong Kong, 12 December 2009. In Journal of the Hong Kong College of Cardiology, 2009, v. 17 n. 2, p. 58, abstract no. P10-

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