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

Result code in 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>

Result on the web

<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>

Result language

angličtina

Original language name

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

Original language description

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.

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

FA - Cardiovascular diseases including cardio-surgery

OECD FORD branch

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Project

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Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2014

Confidentiality

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

Name of the periodical

Cardiovascular Research

ISSN

0008-6363

e-ISSN

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Volume of the periodical

104

Issue of the periodical within the volume

1

Country of publishing house

GB - UNITED KINGDOM

Number of pages

10

Pages from-to

216-225

UT code for WoS article

000343317000022

EID of the result in the Scopus database

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