Voltage-dependent blockade of HERG channels expressed in Xenopus oocytes by external Ca2+ and Mg2+

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dc.contributor.authorHo, WKko
dc.contributor.authorKim, Injuneko
dc.contributor.authorLee, COko
dc.contributor.authorEarm, YEko
dc.date.accessioned2013-03-03T07:33:12Z-
dc.date.available2013-03-03T07:33:12Z-
dc.date.created2012-02-06-
dc.date.created2012-02-06-
dc.date.issued1998-03-
dc.identifier.citationJOURNAL OF PHYSIOLOGY-LONDON, v.507, no.3, pp.631 - 638-
dc.identifier.issn0022-3751-
dc.identifier.urihttp://hdl.handle.net/10203/77791-
dc.description.abstract1. We expressed the human eag-related gene (HERG), which is known to encode the delayed rectifier K+ current (I-Kr) in cardiac muscle, in Xenopus oocytes. Using a two-microelectrode voltage clamp technique, the effect of external Ca2+ and Mg2+ on the HERG current (I-HERG) was investigated. 2. When [Ca2+](o) was increased, the amplitude of outward I-HERG elicited by depolarization decreased, and the rate of current onset slowed. The rate of current decay observed on repolarization was greatly accelerated. The threshold and fully activated potential of I-HERG shifted to a more positive potential. On the other hand, the inactivation property represented by the negative slope of the I-V curve and the instantaneous conductance of I-HERG were little affected by [Ca2+](o). 3. The effect of [Ca2+](o) on I-HERG can be interpreted using the channel blockade model. The blockade is voltage dependent; smaller dissociation constants (K-M) at more negative potentials indicate that block is facilitated by hyperpolarization. K-M changes e-fold for 14.5 mV and the fractional electrical distance of the binding site calculated from this value is 0.86. 4. Blockade by a low concentration of Ca2+ (0.5 mM) was inhibited by increasing [K+](o) (from 2 to 20 mM), whereas blockade by a high concentration of Ca2+ (5 mM) was not affected by varying [K+](o), indicating that there is competition between permeating ions and blocking ions. 5. The effect of [Mg2+](o) on I-HERG was qualitatively similar to that of [Ca2+](o), but the potency was lower. 6. These results suggest that external Ca2+ and Mg2+ block the HERG channel in a voltage-and time-dependent manner, resulting in a voltage dependence which has been regarded as a property of the activation gate.-
dc.languageEnglish-
dc.publisherCAMBRIDGE UNIV PRESS-
dc.subjectPOTASSIUM CHANNEL-
dc.subjectDIVALENT-CATIONS-
dc.subjectSINOATRIAL NODE-
dc.subjectK+ CURRENT-
dc.subjectRECTIFICATION-
dc.subjectCONDUCTANCE-
dc.subjectRECTIFIER-
dc.subjectMODULATION-
dc.subjectMECHANISM-
dc.subjectNEURONS-
dc.titleVoltage-dependent blockade of HERG channels expressed in Xenopus oocytes by external Ca2+ and Mg2+-
dc.typeArticle-
dc.identifier.wosid000072902500002-
dc.identifier.scopusid2-s2.0-0032521120-
dc.type.rimsART-
dc.citation.volume507-
dc.citation.issue3-
dc.citation.beginningpage631-
dc.citation.endingpage638-
dc.citation.publicationnameJOURNAL OF PHYSIOLOGY-LONDON-
dc.identifier.doi10.1111/j.1469-7793.1998.631bs.x-
dc.contributor.localauthorKim, Injune-
dc.contributor.nonIdAuthorHo, WK-
dc.contributor.nonIdAuthorLee, CO-
dc.contributor.nonIdAuthorEarm, YE-
dc.type.journalArticleArticle-
dc.subject.keywordPlusPOTASSIUM CHANNEL-
dc.subject.keywordPlusDIVALENT-CATIONS-
dc.subject.keywordPlusSINOATRIAL NODE-
dc.subject.keywordPlusK+ CURRENT-
dc.subject.keywordPlusRECTIFICATION-
dc.subject.keywordPlusCONDUCTANCE-
dc.subject.keywordPlusRECTIFIER-
dc.subject.keywordPlusMODULATION-
dc.subject.keywordPlusMECHANISM-
dc.subject.keywordPlusNEURONS-
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