Stress increased sodium currents and altered INakinetics
Stress has been recognized as a risk factor of cardiovascular diseases such as Takotsubo cardiomyopathy and arrhythmia (Stiermaier et al., 2015; Templin et al., 2015). Stimulation of βAR located in cardiomyocyte membranes by catecholamines regulates ion channels to maintain normal cardiac function. For instance, stimulation of βAR-Gs signaling pathway enhances peak I Na and the subsequent conductivity and excitability of cardiac myocytes (Aflaki M, 2014; Grinshpon & Bondarenko, 2016; Szentmiklosi AJ, 2015). However, overstimulation of βAR impairs ion channels function causing myocardial injury and abnormal rhythm (Parati & Esler, 2012). This is because excessive upregulation of I NaL increases the risk of arrhythmia (Dybkova N, 2014; Bence Hegyi et al., 2018). In this study, ISO was used as a stimulus to simulate cardiac stress, increasingI NaL and peak I Na, which is consistent with previous studies (Dybkova N, 2014; Bence Hegyi et al., 2018). It was also found that that sodium channel is easily activated but difficult to be inactivated or recover from inactivation after a stress stimulus. Given the lack of effective treatments for ventricular arrhythmias caused by sodium channel dysfunction, it is important to investigate the regulation of sodium currents in order to uncover novel I NaL blockers for the prevention and treatment of arrhythmias (Remme & Wilde, 2014).