A Kir2.1 gain-of-function mutation underlies familial atrial fibrillation

Autor: Jie Lin, Min Xia, Yiping Chen, Yusong He, Zhiwen Pan, Petra M.H. Eurlings, Yanting Zhou, Rongrong Wang, Jacques Barhanin, Saïd Bendahhou, Li Li, Qinshu Zhou, Yi-Han Chen, Marie-Madeleine Larroque, Ban Liu, Qian Zhu, Weiqin Qiu, Qingfeng Jin, Xiongjian Dong, Haiying Wan, Yi Liu, Bo Liang, Wenyuan Xu, Yiqing Yang
Rok vydání: 2005
Předmět:
Male
Models
Molecular
Protein Conformation
DNA Mutational Analysis
Mutant
030204 cardiovascular system & hematology
medicine.disease_cause
Biochemistry
Conserved sequence
0302 clinical medicine
Atrial Fibrillation
Conserved Sequence
Aged
80 and over
Genetics
0303 health sciences
Mutation
Microscopy
Confocal
Reverse Transcriptase Polymerase Chain Reaction
Inward-rectifier potassium ion channel
Kir2.1
Valine
Atrial fibrillation
Middle Aged
Electrophysiology
COS Cells
cardiovascular system
Female
Familial atrial fibrillation
Adult
medicine.medical_specialty
Molecular Sequence Data
Biophysics
Biology
Transfection
Cell Line
03 medical and health sciences
Molecular genetics
Internal medicine
medicine
Animals
Humans
Amino Acid Sequence
Heart Atria
Isoleucine
Potassium Channels
Inwardly Rectifying
Molecular Biology
Aged
030304 developmental biology
Family Health
DNA
Sequence Analysis
DNA
Cell Biology
medicine.disease
Endocrinology
Mutagenesis
Site-Directed
Zdroj: Biochemical and Biophysical Research Communications. 332:1012-1019
ISSN: 0006-291X
Popis: The inward rectifier K(+) channel Kir2.1 mediates the potassium I(K1) current in the heart. It is encoded by KCNJ2 gene that has been linked to Andersen's syndrome. Recently, strong evidences showed that Kir2.1 channels were associated with mouse atrial fibrillation (AF), therefore we hypothesized that KCNJ2 was associated with familial AF. Thirty Chinese AF kindreds were evaluated for mutations in KCNJ2 gene. A valine-to-isoleucine mutation at position 93 (V93I) of Kir2.1 was found in all affected members in one kindred. This valine and its flanking sequence is highly conserved in Kir2.1 proteins among different species. Functional analysis of the V93I mutant demonstrated a gain-of-function consequence on the Kir2.1 current. This effect is opposed to the loss-of-function effect of previously reported mutations in Andersen's syndrome. Kir2.1 V93I mutation may play a role in initiating and/or maintaining AF by increasing the activity of the inward rectifier K(+) channel.
Databáze: OpenAIRE
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