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).