+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Congenital long QT syndrome caused by the F275S KCNQ1 mutation: mechanism of impaired channel function

Congenital long QT syndrome caused by the F275S KCNQ1 mutation: mechanism of impaired channel function

Biochemical and Biophysical Research Communications 380(1): 127-131

Congenital long QT syndrome is characterized by a prolongation of ventricular repolarization and recurrent episodes of life-threatening ventricular tachyarrhythmias, often leading to sudden death. We previously identified a missense mutation F275S located within the S5 transmembrane domain of the KCNQ1 ion channel in a Chinese family with long QT syndrome. We used oocyte expression of the KCNQ1 polypeptide to study the effects of the F275S mutation on channel properties. Expression of the F275 mutant, or co-expression with the wild-type S275 polypeptide, significantly decreased channel current amplitudes. Moreover, the F275S substitution decreased the rates of channel activation and deactivation. In transfected HEK293 cells fluorescence microscopy revealed that the F275S mutation perturbed the subcelluar localization of the ion channel. These results indicate that the F275S KCNQ1 mutation leads to impaired polypeptide trafficking that in turn leads to reduction of channel ion currents and altered gating kinetics.

Please choose payment method:

(PDF emailed within 0-6 h: $19.90)

Accession: 024383280

Download citation: RISBibTeXText

PMID: 19167356

DOI: 10.1016/j.bbrc.2009.01.051

Related references

Impaired ion channel function related to a common KCNQ1 mutation — Implications for risk stratification in long QT syndrome. 2012

Impaired ion channel function related to a common KCNQ1 mutation - implications for risk stratification in long QT syndrome 1. Gene 511(1): 26-33, 2012

A novel KCNQ1 mutation in Chinese with congenital long QT syndrome. Zhonghua Er Ke Za Zhi 41(10): 724-727, 2003

Congenital long-QT syndrome caused by a novel mutation in a conserved acidic domain of the cardiac Na+ channel. Circulation 99(24): 3165-3171, 1999

Biophysical characteristics of a new mutation on the KCNQ1 potassium channel (L251P) causing long QT syndrome. Canadian Journal of Physiology and Pharmacology 81(2): 129-134, 2003

Mutation analysis of potassium channel genes KCNQ1 and KCNH2 in patients with long QT syndrome. Chinese Medical Journal 116(9): 1333-1335, 2003

Mutation analysis in congenital Long QT Syndrome--a case with missense mutations in KCNQ1 and SCN5A. Genetic Testing 7(1): 57-61, 2003

Three generations of hereditary long-QT syndrome with complete penetrance caused by the p.G316E KCNQ1 mutation. Pediatric Cardiology 32(1): 102-104, 2011

A left ventricular noncompaction in a patient with long QT syndrome caused by a KCNQ1 mutation: a case report. Heart and Vessels 28(1): 126-129, 2013

A founder mutation of the potassium channel KCNQ1 in long QT syndrome: Implications for estimation of disease prevalence and molecular diagnostics. Journal of the American College of Cardiology 37(2): 562-568, 2001

Analysis of the KCNQ1 gene mutation in 2 families with congenital long QT syndrome type 1 in Xinjiang Uygur Autonomous Region. Zhonghua Xin Xue Guan Bing Za Zhi 46(11): 868-873, 2018

A double-point mutation in the selectivity filter site of the KCNQ1 potassium channel results in a severe phenotype, LQT1, of long QT syndrome. Journal of Cardiovascular Electrophysiology 19(5): 541-549, 2008

Patients With Long-QT Syndrome Caused by Impaired hERG -Encoded K v 11.1 Potassium Channel Have Exaggerated Endocrine Pancreatic and Incretin Function Associated With Reactive Hypoglycemia. Circulation 135(18): 1705-1719, 2017

Mutations in cytoplasmic loops of the KCNQ1 channel and the risk of life-threatening events: implications for mutation-specific response to β-blocker therapy in type 1 long-QT syndrome. Circulation 125(16): 1988-1996, 2012

EP04.36: Fetal sinus bradycardia as the symptom of previously undiagnosed familial form of Long QT syndrome type 1 caused by mutation of KCNQ1 gene (c.926C>T). Ultrasound in Obstetrics & Gynecology 50: 279-279, 2017