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 |
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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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