PMID- 29573040
OWN - NLM
STAT- MEDLINE
DCOM- 20181011
LR  - 20181011
IS  - 1097-0029 (Electronic)
IS  - 1059-910X (Linking)
VI  - 81
IP  - 6
DP  - 2018 Jun
TI  - F463L increases the potential of dofetilide on human ether-a-go-go-related gene 
      (hERG) channels.
PG  - 663-668
LID - 10.1002/jemt.23021 [doi]
AB  - Mutations in genes related to long QT syndrome (LQTS) is recognized as an 
      independent risk of drug-induced LQTS. We previously screened a mutation F463L in 
      a Chinese patient with LQT2, syncope, and epilepsy. Here, we planned to 
      illustrate how F463L influences the action of dofetilide on hERG channels. 
      F463L-hERG plasmids were transfected into the stable Human Embryonic Kidney 293 
      (HEK293) cells expressing WT-hERG to generate heterozygous mutant 
      (WT + F463L-hERG). Whole-cell patch clamp and laser confocal scanning microscopy 
      were used to evaluate electrophysiological consequences and the membrane 
      distribution of hERG protein. In comparison of WT-hERG channels exposed to 
      dofetilide, heterozygous F463L-hERG channels showed a reduction in the density of 
      tail currents when exposed amidarone. F463L-hERG also altered the action of 
      dofetilide on the gating properties of hERG channels. Images of 
      dofetilide-treated cells expressing heterozygous F463L showed a severe retention 
      and reduction of protein expression on the membrane compared to WT. In 
      conclusion, dofetilide displays a powerful inhibitory effect on the currents from 
      cells expressing heterozygous F463L, thus showing an additive suppression of 
      currents by F463L with dofetilide.
CI  - (c) 2018 Wiley Periodicals, Inc.
FAU - Cheng, Gong
AU  - Cheng G
AUID- ORCID: 0000-0001-7824-3916
AD  - Department of Cardiovascular Medicine, the First Affiliated Hospital of Xi'an 
      Jiaotong University, Xi'an, Shaanxi, 710061, P.R.
AD  - Cardiovascular Medicine, Shaanxi Provincial People's Hospital of Xi'an Jiaotong 
      University, Xi'an, Shaanxi, 710068, China.
FAU - Wu, Jine
AU  - Wu J
AD  - Department of Cardiovascular Medicine, the First Affiliated Hospital of Xi'an 
      Jiaotong University, Xi'an, Shaanxi, 710061, P.R.
FAU - Han, Wenqi
AU  - Han W
AD  - Department of Cardiovascular Medicine, the First Affiliated Hospital of Xi'an 
      Jiaotong University, Xi'an, Shaanxi, 710061, P.R.
FAU - Sun, Chaofeng
AU  - Sun C
AD  - Department of Cardiovascular Medicine, the First Affiliated Hospital of Xi'an 
      Jiaotong University, Xi'an, Shaanxi, 710061, P.R.
LA  - eng
PT  - Journal Article
DEP - 20180323
PL  - United States
TA  - Microsc Res Tech
JT  - Microscopy research and technique
JID - 9203012
RN  - 0 (Ether-A-Go-Go Potassium Channels)
RN  - 0 (Phenethylamines)
RN  - 0 (Potassium Channel Blockers)
RN  - 0 (Sulfonamides)
RN  - R4Z9X1N2ND (dofetilide)
SB  - IM
MH  - Cell Line
MH  - Ether-A-Go-Go Potassium Channels/*genetics/*metabolism
MH  - HEK293 Cells
MH  - Humans
MH  - Long QT Syndrome/*genetics
MH  - Microscopy, Confocal
MH  - Mutation/genetics
MH  - Patch-Clamp Techniques
MH  - Phenethylamines/*pharmacology
MH  - Plasmids/genetics
MH  - Potassium Channel Blockers/*pharmacology
MH  - Sulfonamides/*pharmacology
OTO - NOTNLM
OT  - Dofetilide
OT  - drug-induced LQTS
OT  - hERG gene
OT  - mutation
OT  - whole-cell patch
EDAT- 2018/03/25 06:00
MHDA- 2018/10/12 06:00
CRDT- 2018/03/25 06:00
PHST- 2017/09/19 00:00 [received]
PHST- 2018/02/02 00:00 [revised]
PHST- 2018/03/02 00:00 [accepted]
PHST- 2018/03/25 06:00 [pubmed]
PHST- 2018/10/12 06:00 [medline]
PHST- 2018/03/25 06:00 [entrez]
AID - 10.1002/jemt.23021 [doi]
PST - ppublish
SO  - Microsc Res Tech. 2018 Jun;81(6):663-668. doi: 10.1002/jemt.23021. Epub 2018 Mar 
      23.