Referenced in: none

Automatically associated channels: Kir2.1 , Kir2.3

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

Authors: 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

Journal, date & volume: Biochem. Biophys. Res. Commun., 2005 Jul 15 , 332, 1012-9

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/15922306

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.