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dc.contributor.authorChen, Muen_US
dc.contributor.authorXu, Dong-Zhuen_US
dc.contributor.authorWu, Adonis Z.en_US
dc.contributor.authorGuo, Shuaien_US
dc.contributor.authorWan, Juyien_US
dc.contributor.authorYin, Dechunen_US
dc.contributor.authorLin, Shien-Fongen_US
dc.contributor.authorChen, Zhenhuien_US
dc.contributor.authorRubart-von der Lohe, Michaelen_US
dc.contributor.authorEverett, Thomas H.en_US
dc.contributor.authorQu, Zhilinen_US
dc.contributor.authorWeiss, James N.en_US
dc.contributor.authorChen, Peng-Shengen_US
dc.date.accessioned2019-04-02T05:59:12Z-
dc.date.available2019-04-02T05:59:12Z-
dc.date.issued2018-11-15en_US
dc.identifier.issn2379-3708en_US
dc.identifier.urihttp://dx.doi.org/10.1172/jci.insight.122329en_US
dc.identifier.urihttp://hdl.handle.net/11536/148474-
dc.description.abstractThe mechanisms of J wave syndrome (JWS) are incompletely understood. Here, we showed that the concomitant activation of small-conductance calcium-activated potassium (SK) current (I-KAS) and inhibition of sodium current by cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine (CyPPA) recapitulate the phenotypes of JWS in Langendorff-perfused rabbit hearts. CyPPA induced significant J wave elevation and frequent spontaneous ventricular fibrillation (SVF), as well as sinus bradycardia, atrioventricular block, and intraventricular conduction delay. I-KAS activation by CyPPA resulted in heterogeneous shortening of action potential (AP) duration (APD) and repolarization alternans. CyPPA inhibited cardiac sodium current (I-Na) and decelerated AP upstroke and intracellular calcium transient. SVFs were typically triggered by short-coupled premature ventricular contractions, initiated with phase 2 reentry and originated more frequently from the right than the left ventricles. Subsequent I-KAS blockade by apamin reduced J wave elevation and eliminated SVF. beta-Adrenergic stimulation was antiarrhythmic in CyPPA-induced electrical storm. Like CyPPA, hypothermia (32.0 degrees C) also induced J wave elevation and SVF. It facilitated negative calcium-voltage coupling and phase 2 repolarization alternans with spatial and electromechanical discordance, which were ameliorated by apamin. These findings suggest that I-KAS activation contributes to the development of JWS in rabbit ventricles.en_US
dc.language.isoen_USen_US
dc.titleConcomitant SK current activation and sodium current inhibition cause J wave syndromeen_US
dc.typeArticleen_US
dc.identifier.doi10.1172/jci.insight.122329en_US
dc.identifier.journalJCI INSIGHTen_US
dc.citation.volume3en_US
dc.contributor.department生醫工程研究所zh_TW
dc.contributor.departmentInstitute of Biomedical Engineeringen_US
dc.identifier.wosnumberWOS:000450338900005en_US
dc.citation.woscount0en_US
Appears in Collections:Articles