Glycine/Serine Polymorphism at Position 38 Influences KCNE1 Subunit’s Modulatory Actions on Rapid and Slow Delayed Rectifier K&lt;sup&gt;+&lt;/sup&gt; Currents

Yamaguchi, Yoshiaki; Nishide, Kohki; Kato, Mario; Hata, Yukiko; Mizumaki, Koichi; Kinoshita, Koshi; Nonobe, Yuki; Tabata, Toshihide; Sakamoto, Tamotsu; Kataoka, Naoya; Nakatani, Yosuke; Ichida, Fukiko; Mori, Hisashi; Fukurotani, Kenkichi; Inoue, Hiroshi; Nishida, Naoki

doi:10.1253/circj.cj-13-1126

Cited by 11 publications

(11 citation statements)

References 34 publications

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“…1 hERG co-expression with the minor 38S KCNE1 polymorphism increased the sensitivity of reactivation (recovery from inactivation) kinetics to hypokalemia. 1 The hERG results in their study are consistent with a modest depression of IKr in a setting of homozygous KCNE1-38S and, potentially, to differential effects of IKr blockade between the major and minor KCNE1 polymorphisms studied.…”

Section: To the Editorsupporting

confidence: 52%

“…The results of this new study 1 highlight that consideration should not necessarily be limited to IKs; additional potential contributory factors are a reduction in IKr amplitude and increased sensitivity of IKr to pharmacological blockade. E-4031 is an experimental rather than clinically used drug, but is struc-…”

Section: To the Editormentioning

confidence: 85%

“…KCNE1-38S produced a positive shift in voltage-dependent activation of KCNQ1+KCNE1, compared to KCNQ1+KCNE1-38G. 1 Of particular note, however, are the differences reported between the 2 polymorphisms when coexpressed with hERG. With a conventional voltage-clamp protocol, hERG current magnitude was significantly smaller for hERG+KCNE1-38S than with KCNE1-38G at potentials of −20 mV and more positive, without any accompanying shift in the voltage-dependence of activation.…”

Section: To the Editormentioning

confidence: 99%

See 2 more Smart Citations

Modification of KCNH2-Encoded Cardiac Potassium Channels by KCNE1 Polymorphism

Hancox

Harchi

et al. 2014

Circ J

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Section: To the Editorsupporting

confidence: 52%

Section: To the Editormentioning

confidence: 85%

Section: To the Editormentioning

confidence: 99%

See 1 more Smart Citation

Modification of KCNH2-Encoded Cardiac Potassium Channels by KCNE1 Polymorphism

Hancox

Harchi

et al. 2014

Circ J

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“…Several genetic variations directly or indirectly affecting hERG channel function are related to arrhythmic disorders induced by class III antiarrhythmic drugs or hypokalemia. [6][7][8] We compared the effects of these arrhythmogenic factors on hERG(WT) and hERG(G487R) channel currents in HEK-293T cells. These results provide the scaffolding for designing treatment programs for hERG(G487R) carriers.…”

Section: )mentioning

confidence: 99%

The Susceptibilities of Human Ether-à-Go-Go-Related Gene Channel with the G487R Mutation to Arrhythmogenic Factors

Hisajima

Hata

Kinoshita

et al. 2015

Biological & Pharmaceutical Bulletin

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The human ether-à-go-go-related gene (hERG) channel mediates the rapid delayed rectifier potassium current (I Kr ) responsible for shaping the repolarization phase of cardiac action potentials. hERG mutation may cause hERG channel malfunction, leading to long QT syndrome and other arrhythmic disorders. Elucidation of the genotype-phenotype relationships of individual hERG mutations is key to the development of treatment for such arrhythmic disorders. We previously identified hERG(G487R), a missense mutant with a glycine-to-arginine substitution at position 487. In the absence of arrhythmogenic factors, hERG(G487R) subunit-containing channels show normal surface expression and gating kinetics. However, it remains unknown whether the mutation exacerbates hERG channel malfunction induced by arrhythmogenic factors. Here we used a voltage-clamp technique to compare the effects of the major arrythmogenic factors on wildtype hERG [hERG(WT)] and hERG(G487R) channel currents (I hERG ) in HEK-293T cells. The extent of I hERGblockade by the antiarrhythmic drug dofetilide or E4031 was not different between these channels. On the other hand, the extracellular K concentration ([K ] ex )-dependent changes in the rates of recovery from inactivation and deactivation of I hERG were rather less obvious for hERG(G487R) channel than for hERG(WT) channel. These findings suggest that the inheritance of hERG(G487R) does not increase the risk of arrhythmic disorders induced by antiarrhythmic drugs or hypokalemia.

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“…1 As compared with KCNE1 (38G), co-expression of KCNE1 (38S) increases the susceptibility to E-4031, an experimental class III antiarrhythmic drug, lowering the apparent dissociation constant to 1/4. 2 The effects differ considerably, depending on the type of KCNE1 mutants/ variant and drug.…”

mentioning

confidence: 99%

Modification of KCNH2-Encoded Cardiac Potassium Channels by KCNE1 Polymorphism

Tabata

Yamaguchi

Hata

et al. 2014

Circ J

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Glycine/Serine Polymorphism at Position 38 Influences KCNE1 Subunit’s Modulatory Actions on Rapid and Slow Delayed Rectifier K<sup>+</sup> Currents

Cited by 11 publications

References 34 publications

Modification of <i>KCNH2</i>-Encoded Cardiac Potassium Channels by KCNE1 Polymorphism

Modification of <i>KCNH2</i>-Encoded Cardiac Potassium Channels by KCNE1 Polymorphism

The Susceptibilities of Human Ether-à-Go-Go-Related Gene Channel with the G487R Mutation to Arrhythmogenic Factors

Modification of <i>KCNH2</i>-Encoded Cardiac Potassium Channels by KCNE1 Polymorphism

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