The E23K variant of the Kir6.2 subunit of the ATP-sensitive potassium channel increases susceptibility to ventricular arrhythmia in response to ischemia in rats

Background: 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. Methods: Transgenic rats were generated to express human E23K-variant genomic DNA in the heart under the a-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. Results: 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(70), APD(90) 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. Conclusion: The E23K variant of the KATP channel increased the susceptibility to ventricular arrhythmia under acute ischemia stress. (C) 2017 Elsevier Ireland Ltd. All rights reserved.