Long-QT mutation p.K557E-Kv7.1: dominant-negative suppression of I-Ks, but preserved cAMP-dependent up-regulation

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14110%2F14%3A00076953" target="_blank" >RIV/00216224:14110/14:00076953 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1093/cvr/cvu191" target="_blank" >http://dx.doi.org/10.1093/cvr/cvu191</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1093/cvr/cvu191" target="_blank" >10.1093/cvr/cvu191</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Long-QT mutation p.K557E-Kv7.1: dominant-negative suppression of I-Ks, but preserved cAMP-dependent up-regulation

Popis výsledku v původním jazyce

Aims Mutations in KCNQ1, encoding for Kv7.1, the alpha-subunit of the I-Ks channel, cause long-QT syndrome type 1, potentially predisposing patients to ventricular tachyarrhythmias and sudden cardiac death, in particular, during elevated sympathetic tone. Here, we aim at characterizing the p.Lys557Glu (K557E) Kv7.1 mutation, identified in a Dutch kindred, at baseline and during (mimicked) increased adrenergic tone. Methods and results K557E carriers had moderate QTc prolongation that augmented significantly during exercise. I-Ks characteristics were determined after co-expressing Kv7.1-wild-type (WT) and/or K557E with minK and Yotiao in Chinese hamster ovary cells. K557E caused I-Ks loss of function with slowing of the activation kinetics, accelerationof deactivation kinetics, and a rightward shift of voltage-dependent activation. Together, these contributed to a dominant-negative reduction in I-Ks density.

Název v anglickém jazyce

Long-QT mutation p.K557E-Kv7.1: dominant-negative suppression of I-Ks, but preserved cAMP-dependent up-regulation

Popis výsledku anglicky

Aims Mutations in KCNQ1, encoding for Kv7.1, the alpha-subunit of the I-Ks channel, cause long-QT syndrome type 1, potentially predisposing patients to ventricular tachyarrhythmias and sudden cardiac death, in particular, during elevated sympathetic tone. Here, we aim at characterizing the p.Lys557Glu (K557E) Kv7.1 mutation, identified in a Dutch kindred, at baseline and during (mimicked) increased adrenergic tone. Methods and results K557E carriers had moderate QTc prolongation that augmented significantly during exercise. I-Ks characteristics were determined after co-expressing Kv7.1-wild-type (WT) and/or K557E with minK and Yotiao in Chinese hamster ovary cells. K557E caused I-Ks loss of function with slowing of the activation kinetics, accelerationof deactivation kinetics, and a rightward shift of voltage-dependent activation. Together, these contributed to a dominant-negative reduction in I-Ks density.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

FA - Kardiovaskulární nemoci včetně kardiochirurgie

OECD FORD obor

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Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2014

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Cardiovascular Research

ISSN

0008-6363

e-ISSN

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Svazek periodika

104

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

10

Strana od-do

216-225

Kód UT WoS článku

000343317000022

EID výsledku v databázi Scopus

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