Open AccessMost LQT2 Mutations Reduce Kv11.1 (hERG) Current by a Class 2 (Trafficking-Deficient) Mechanism
Author(s) -
Corey L. Anderson,
Brian P. Delisle,
Blake D. Anson,
Jennifer A. Kilby,
Melissa L. Will,
David J. Tester,
Qiuming Gong,
Zhengfeng Zhou,
Michael J. Ackerman,
Craig T. January
Publication year - 2006
Publication title -
circulation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.795
H-Index - 607
eISSN - 1524-4539
pISSN - 0009-7322
DOI - 10.1161/circulationaha.105.570200
Subject(s) - herg , missense mutation , phenotype , hek 293 cells , mutation , microbiology and biotechnology , long qt syndrome , genetics , medicine , biology , potassium channel , gene , qt interval
The KCNH2 or human ether-a-go-go related gene (hERG) encodes the Kv11.1 alpha-subunit of the rapidly activating delayed rectifier K+ current (IKr) in the heart. Type 2 congenital long-QT syndrome (LQT2) results from KCNH2 mutations that cause loss of Kv11.1 channel function. Several mechanisms have been identified, including disruption of Kv11.1 channel synthesis (class 1), protein trafficking (class 2), gating (class 3), or permeation (class 4). For a few class 2 LQT2-Kv11.1 channels, it is possible to increase surface membrane expression of Kv11.1 current (IKv11.1). We tested the hypotheses that (1) most LQT2 missense mutations generate trafficking-deficient Kv11.1 channels, and (2) their trafficking-deficient phenotype can be corrected.
Accelerating Research
Robert Robinson Avenue,
Oxford Science Park, Oxford
OX4 4GP, United Kingdom
Address
John Eccles HouseRobert Robinson Avenue,
Oxford Science Park, Oxford
OX4 4GP, United Kingdom