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

Min Xia; Qingfeng Jin; Saïd Bendahhou; Yusong He; Marie-Madeleine Larroque; Yiping Chen; Qinshu Zhou; Yiqing Yang; Yi Liu; Ban Liu; Qian Zhu; Yanting Zhou; Jie Lin; Bo Liang; Li Li; Xiongjian Dong; Zhiwen Pan; Rongrong Wang; Haiying Wan; Weiqin Qiu; Wenyuan Xu; Petra Eurlings; Jacques Barhanin; Yihan Chen

doi:10.1016/j.bbrc.2005.05.054

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

Min Xia, Qingfeng Jin, Saïd Bendahhou, Yusong He, Marie-Madeleine Larroque, Yiping Chen, Qinshu Zhou, Yiqing Yang, Yi Liu, Ban Liu, Qian Zhu, Yanting Zhou, Jie Lin, Bo Liang, Li Li, Xiongjian Dong, Zhiwen Pan, Rongrong Wang, Haiying Wan, Weiqin QiuWenyuan Xu, Petra Eurlings, Jacques Barhanin, Yihan Chen

Physiology of circulation, kidney and lung

294 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Biochemical and Biophysical Research Communications
Volume	332
Issue number	4
Pages (from-to)	1012-9
Number of pages	8
ISSN	0006-291X
DOIs	https://doi.org/10.1016/j.bbrc.2005.05.054
Publication status	Published - 2005

Keywords

Adult
Aged
Aged, 80 and over
Amino Acid Sequence
Animals
Atrial Fibrillation
COS Cells
Cell Line
Conserved Sequence
DNA
DNA Mutational Analysis
Electrophysiology
Family Health
Female
Heart Atria
Humans
Isoleucine
Male
Microscopy, Confocal
Middle Aged
Models, Molecular
Molecular Sequence Data
Mutagenesis, Site-Directed
Mutation
Potassium Channels, Inwardly Rectifying
Protein Conformation
Reverse Transcriptase Polymerase Chain Reaction
Sequence Analysis, DNA
Transfection
Valine

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10.1016/j.bbrc.2005.05.054

A Kir2.1 gain-of-function mutation underlies familial atrial fibrillationFinal published version, 577 KB

http://www.sciencedirect.com/science/article/pii/S0006291X0501020X

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Xia, M., Jin, Q., Bendahhou, S., He, Y., Larroque, M-M., Chen, Y., Zhou, Q., Yang, Y., Liu, Y., Liu, B., Zhu, Q., Zhou, Y., Lin, J., Liang, B., Li, L., Dong, X., Pan, Z., Wang, R., Wan, H., ... Chen, Y. (2005). A Kir2.1 gain-of-function mutation underlies familial atrial fibrillation. Biochemical and Biophysical Research Communications, 332(4), 1012-9. https://doi.org/10.1016/j.bbrc.2005.05.054

Xia, M, Jin, Q, Bendahhou, S, He, Y, Larroque, M-M, Chen, Y, Zhou, Q, Yang, Y, Liu, Y, Liu, B, Zhu, Q, Zhou, Y, Lin, J, Liang, B, Li, L, Dong, X, Pan, Z, Wang, R, Wan, H, Qiu, W, Xu, W, Eurlings, P, Barhanin, J & Chen, Y 2005, 'A Kir2.1 gain-of-function mutation underlies familial atrial fibrillation', Biochemical and Biophysical Research Communications, vol. 332, no. 4, pp. 1012-9. https://doi.org/10.1016/j.bbrc.2005.05.054

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abstract = "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.",

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TY - JOUR

T1 - A Kir2.1 gain-of-function mutation underlies familial atrial fibrillation

AU - Xia, Min

AU - Jin, Qingfeng

AU - Bendahhou, Saïd

AU - He, Yusong

AU - Larroque, Marie-Madeleine

AU - Chen, Yiping

AU - Zhou, Qinshu

AU - Yang, Yiqing

AU - Liu, Yi

AU - Liu, Ban

AU - Zhu, Qian

AU - Zhou, Yanting

AU - Lin, Jie

AU - Liang, Bo

AU - Li, Li

AU - Dong, Xiongjian

AU - Pan, Zhiwen

AU - Wang, Rongrong

AU - Wan, Haiying

AU - Qiu, Weiqin

AU - Xu, Wenyuan

AU - Eurlings, Petra

AU - Barhanin, Jacques

AU - Chen, Yihan

PY - 2005

Y1 - 2005

N2 - 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.

AB - 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.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Amino Acid Sequence

KW - Animals

KW - Atrial Fibrillation

KW - COS Cells

KW - Cell Line

KW - Conserved Sequence

KW - DNA

KW - DNA Mutational Analysis

KW - Electrophysiology

KW - Family Health

KW - Female

KW - Heart Atria

KW - Humans

KW - Isoleucine

KW - Male

KW - Microscopy, Confocal

KW - Middle Aged

KW - Models, Molecular

KW - Molecular Sequence Data

KW - Mutagenesis, Site-Directed

KW - Mutation

KW - Potassium Channels, Inwardly Rectifying

KW - Protein Conformation

KW - Reverse Transcriptase Polymerase Chain Reaction

KW - Sequence Analysis, DNA

KW - Transfection

KW - Valine

U2 - 10.1016/j.bbrc.2005.05.054

DO - 10.1016/j.bbrc.2005.05.054

M3 - Journal article

C2 - 15922306

SN - 0006-291X

VL - 332

SP - 1012

EP - 1019

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

IS - 4

ER -

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

Abstract

Keywords

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