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Characterization of S818L mutation in HERG C‐terminus in LQT2
Author(s) -
Nakajima Tadashi,
Kurabayashi Masahiko,
Ohyama Yoshio,
Kaneko Yoshiaki,
Furukawa Tetsushi,
Itoh Toshio,
Taniguchi Yasuhiro,
Tanaka Toshihiro,
Nakamura Yusuke,
Hiraoka Masayasu,
Nagai Ryozo
Publication year - 2000
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(00)01988-8
Subject(s) - herg , mutation , chemistry , genetics , microbiology and biotechnology , pharmacology , biology , medicine , gene , potassium channel
We examined the mechanism(s) for HERG channel dysfunction in an S818L mutation in the HERG C‐terminus using the heterologous expression system in Xenopus oocytes. Injection of S818L cRNA alone did not produce expressed currents. Coinjection of an equal amount of S818L cRNA with wild‐type (WT) cRNA into oocytes did not exhibit apparent dominant‐negative suppression. However, coinjection of excess amounts of S818L cRNAs with WT cRNA into oocytes decreased HERG current amplitudes and shifted the voltage dependence of activation to negative potentials, accelerated its activation and deactivation. The data suggest that S818L alone cannot form functional channels, whereas S818L subunits can, at least in part, coassemble with WT subunits to form heterotetrameric functional channels, and imply that the HERG C‐terminus may contain a domain involving the activation–deactivation process of the channel. These findings may provide new insights into the structure–function relationships of the HERG C‐terminus.