Feng Ying, Liu Jianfang, Wang Menglong, Liu Menglin, Shi Lei, Yuan Wenhui, Ye Jing, Hu Dan, Wan Jun
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, China; Hubei Key Laboratory of Cardiology, Wuhan 430060, China; Department of Emergency Medicine, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China.
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, China; Hubei Key Laboratory of Cardiology, Wuhan 430060, China.
Int J Cardiol. 2017 Apr 1;232:192-198. doi: 10.1016/j.ijcard.2017.01.022. Epub 2017 Jan 4.
The E23K variant of the Kir6.2 subunit of the ATP-sensitive potassium (KATP) channel has been implicated in cardiac remodeling. However, the effects of E23K variant on ventricular electrophysiology and arrhythmogenesis remain unclear.
Transgenic rats were generated to express human E23K-variant genomic DNA in the heart under the α-myosin heavy chain promoter. Electrophysiological parameters including electrocardiograph, ventricular action potential duration (APD), effective refractory period (ERP), electrical alternans and ventricle arrhythmia threshold were examined in wild type (WT) and transgenic rats. The KATP current in cardiomyocytes was recorded using whole-cell patch clamp techniques.
No differences in the electrophysiological parameters between the two groups were found at baseline. However, after acute ischemic stress, shortened QT intervals were further aggravated in the E23K-variant rats. Additionally, the E23K variant exacerbated the decrease of APD, APD and ERP. The ventricular arrhythmia and alternans thresholds were significantly attenuated, and the duration of ventricular arrhythmia induced by electrical stimulation was significantly prolonged in the E23K-variant rats. More importantly, the KATP current in cardiomyocytes was significantly increased in the E23K-variant rats after ischemia.
The E23K variant of the KATP channel increased the susceptibility to ventricular arrhythmia under acute ischemia stress.
ATP敏感性钾（KATP）通道Kir6.2亚基的E23K变体与心脏重塑有关。然而，E23K变体对心室电生理和心律失常发生的影响仍不清楚。
构建转基因大鼠，使其在α-肌球蛋白重链启动子的驱动下在心脏中表达人E23K变体基因组DNA。检测野生型（WT）和转基因大鼠的电生理参数，包括心电图、心室动作电位时程（APD）、有效不应期（ERP）、电交替和心室心律失常阈值。采用全细胞膜片钳技术记录心肌细胞中的KATP电流。
两组在基线时电生理参数无差异。然而，急性缺血应激后，E23K变体大鼠QT间期缩短进一步加重。此外，E23K变体加剧了APD、APD和ERP的降低。E23K变体大鼠的室性心律失常和交替阈值显著降低，电刺激诱发的室性心律失常持续时间显著延长。更重要的是，缺血后E23K变体大鼠心肌细胞中的KATP电流显著增加。
KATP通道的E23K变体在急性缺血应激下增加了室性心律失常的易感性。
