The G314S KCNQ1 mutation exerts a dominant-negative effect on expression of KCNQ1 channels in oocytes.
Congenital long QT syndrome is a cardiac disorder characterized by prolongation of QT interval on the surface ECG associated with syncopal attacks and a high risk of sudden death. Mutations in the voltage-gated potassium channel subunit KCNQ1 induce the most common form of long QT syndrome (LQT1). We previously identified a hot spot mutation G314S located within the pore region of the KCNQ1 ion channel in a Chinese family with long QT syndrome. In the present study, we used oocyte expression of the KCNQ1 polypeptide to study the effects of the G314S mutation on channel properties. The results of electrophysiological studies indicate G314S, co-expressed with KCNE1 was unable to assemble to form active channel. G314S, co-expressed with WT KCNQ1 and KCNE1, suppressed I(ks) currents in a dominant-negative manner, which is consistent with long QT syndrome in the members of the Chinese family carrying G314S KCNQ1 mutation.
Li
Wei
W
Department of Gerontology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
Du
Rong
R
Wang
Qiu-Fen
QF
Tian
Li
L
Yang
Jun-Guo
JG
Song
Zi-Fang
ZF
D000200:Action Potentials / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D055724:Electrophysiological Phenomena; D005799:Genes, Dominant; D005998:Glycine / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051657:KCNQ1 Potassium Channel / Q000235:genetics* / Q000378:metabolism*; D008133:Long QT Syndrome / Q000235:genetics* / Q000503:physiopathology*; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D009865:Oocytes; D012694:Serine / Q000235:genetics / Q000378:metabolism; D014981:Xenopus
D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D012694:Serine; D005998:Glycine