A Kir2.1 gain-of-function mutation underlies familial atrial fibrillation
Copyright policy )A Kir2.1 gain-of-function mutation underlies familial atrial fibrillation
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.
- University of Copenhagen Denmark
- Case Western Reserve University United States
- University of Copenhagen Denmark
- Institut des Sciences Biologiques France
- Centre national de la recherche scientifique France
Adult, Male, Potassium Channels, Protein Conformation, Molecular Sequence Data, DNA Mutational Analysis, Transfection, Cell Line, Models, Atrial Fibrillation, 80 and over, Site-Directed, Animals, Humans, Amino Acid Sequence, Heart Atria, Isoleucine, Conserved Sequence, Aged, Aged, 80 and over, Family Health, Microscopy, Microscopy, Confocal, Reverse Transcriptase Polymerase Chain Reaction, Molecular, Valine, DNA, Middle Aged, Inwardly Rectifying, Electrophysiology, Mutagenesis, Confocal, Mutation, COS Cells, Female, Sequence Analysis
Adult, Male, Potassium Channels, Protein Conformation, Molecular Sequence Data, DNA Mutational Analysis, Transfection, Cell Line, Models, Atrial Fibrillation, 80 and over, Site-Directed, Animals, Humans, Amino Acid Sequence, Heart Atria, Isoleucine, Conserved Sequence, Aged, Aged, 80 and over, Family Health, Microscopy, Microscopy, Confocal, Reverse Transcriptase Polymerase Chain Reaction, Molecular, Valine, DNA, Middle Aged, Inwardly Rectifying, Electrophysiology, Mutagenesis, Confocal, Mutation, COS Cells, Female, Sequence Analysis
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