Electrophysiological analyses of transgenic mice overexpressing KCNJ8 with S422L mutation in cardiomyocytes.
Electrophysiological analyses of transgenic mice overexpressing KCNJ8 with S422L mutation in cardiomyocytes.
复制标题
心肌细胞中过表达具有 S422L 突变的 KCNJ8 的转基因小鼠的电生理分析。
DOI：
10.1016/j.jphs.2017.08.009
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发表时间：
2017
期刊：
影响因子：
3.5
通讯作者：
Nakaya H.
中科院分区：
文献类型：
--
作者：
Watanabe Y;Matsumoto A;Miki T;Seino S;Anzai N;Nakaya H.
KCNJ8的基因分析表明，突变(S422L)是J波综合征(JWS)的易感基因。体外表达研究表明，带有S422L突变的K+(KATP)通道功能增强，对ATP的敏感性降低。然而，KCNJ8在体内的电生理影响尚未阐明。为了研究KCNJ8在心肌细胞中的作用及S422L变异体对心脏电生理的影响，建立了在心肌细胞中高表达KCNJ8S422L变异体(TGmt)或WT(TGWT)的转基因小鼠株系。这些Tg株表现出明显的心电图J-ST段改变，QT显著延长，这可能是由于心室肌细胞电压依赖性K+电流减少导致动作电位延长所致。吡那地尔引起的KATP电流在TG和非TG(WT)心肌细胞之间无明显差异，但TG和非TG(WT)心肌细胞KATP通道的开放概率明显低于非TG(WT)。这些具有明显心电图改变的转基因小鼠表明KCNJ8基因S422L突变不是JWS的直接原因。
Genetic analysis ofKCNJ8has pointed a mutation (S422L) as a susceptible link to J wave syndrome (JWS).In vitroexpression study indicated that the ATP-sensitive K+(KATP) channel with the S422L mutation has the gain-of-function with reduced sensitivity to ATP. However, the electrophysiological impact ofKCNJ8has not been elucidatedin vivo. Transgenic mouse strains overexpressingKCNJ8S422L variant (TGmt) or WT (TGWT) in cardiomyocytes have been created to investigate the influence ofKCNJ8in cardiomyocytes and the JWS-related feature of the S422L variant on the cardiac electrophysiology. These TG strains demonstrated distinct changes in the J-ST segment of ECG with marked QT prolongation, which might be ascribed to the action potential prolongation resulting from the reduction of voltage-dependent K+currents in ventricular cells. The pinacidil-induced KATPcurrent was decreased in these TG myocytes and no obvious difference between TG and non-TG (WT) myocytes in the ATP sensitivity of the KATPchannel was observed although the open probability of the KATPchannels was significantly lower in TG myocytes than WT. These transgenic mouse strains with distinct ECG changes suggested that the S422L mutation inKCNJ8gene is not a direct cause of JWS.
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影响因子：
5.5
作者：
Barajas-Martinez, Hector;Hu, Dan;Ferrer, Tania;Onetti, Carlos G.;Wu, Yuesheng;Burashnikov, Elena;Boyle, Madalene;Surman, Tyler;Urrutia, Janire;Veltmann, Christian;Schimpf, Rainer;Borggrefe, Martin;Wolpert, Christian;Ibrahim, Bassiema B.;Antonio Sanchez-Chapula, Jose;Winters, Stephen;Haissaguerre, Michel;Antzelevitch, Charles
通讯作者：
Antzelevitch, Charles
DOI：
10.1253/circj.cj-12-0284
发表时间：
2012
期刊：
Circulation journal : official journal of the Japanese Circulation Society
影响因子：
--
作者：
Antzelevitch C
通讯作者：
Antzelevitch C
影响因子：
82.9
作者：
Miki, T;Suzuki, M;Seino, S
通讯作者：
Seino, S
影响因子：
4.5
作者：
Kono, Y;Horie, M;Sasayama, S
通讯作者：
Sasayama, S