Document Detail

L539fs/47, a Truncated Mutation of hERG, Decreases hERG Ion Channel Currents in HEK 293 Cells.
MedLine Citation:
PMID:  23134353     Owner:  NLM     Status:  Publisher    
Mutations in human ether-a-go-go-related gene (hERG) are responsible for congenital type-2 long QT syndrome (LQT2). We previously reported a truncated mutation of hERG, L539fs/47, which is composed of a 19 bp deletion mutation and a polymorphism A1692G in a Chinese family with LQT2. This mutation was found to cause a LQT2 phenotype. The objective of this project is to study the functional role of L539fs/47 at the cellular level and its potential contribution to the loss of function in hERG channels. The function of the truncated mutation L539fs/47 was evaluated by constructing a mutated plasmid, transfection of the mutated cDNA into HEK293 cells, and subsequent experiments using patch clamp, Western blotting, and immunostaining. Homologous expression of L539fs/47 in HEK293 cells produced a non-functional protein that could be detected in the cell membrane. When L539fs/47 was simultaneously expressed with wild type (WT) hERG, it suppressed WT hERG currents in a dose-dependent manner and changed the gating properties of the channel. L539fs/47 hERG proteins were detected on the plasma membrane but it failed to generate hERG currents. In general, L539fs/47 decreases the currents of hERG ion channels and suppressed WT channel function in a dose-dependent manner. This may partially explain the clinical manifestations of LQT2 in this family. © 2012 The Authors Clinical and Experimental Pharmacology and Physiology © 2012 Wiley Publishing Asia Pty Ltd.
Aifeng Zhang; Chaofeng Sun; Li Zhang; Ying Lv; Xiaolin Xue; Changcong Cui; Gan-Xin Yan
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-8
Journal Detail:
Title:  Clinical and experimental pharmacology & physiology     Volume:  -     ISSN:  1440-1681     ISO Abbreviation:  Clin. Exp. Pharmacol. Physiol.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0425076     Medline TA:  Clin Exp Pharmacol Physiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2012 The Authors Clinical and Experimental Pharmacology and Physiology © 2012 Wiley Publishing Asia Pty Ltd.
Department of Cardiology, The First Affiliated Hospital, Ion Channel Disease Laboratory, Key Laboratory of Environment and Genes related to Diseases, Ministry of Education, Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China; Department of Cardiology, The Second Affiliated Hospital, Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi, 710004, China.
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