Attenuation of ischemia/reperfusion-induced inhibition of the rapid component of delayed rectifier potassium current by Isosteviol through scavenging reactive oxygen species

Isosteviol has been demonstrated to play a protective role during ischemia reperfusion (I/R) myocardial infarction. However, the underlying electrophysiological mechanisms of isosteviol are still unknown. Our previous study showed that the rapid component of the delayed rectifier potassium channel (I Kr ) plays an important role in the prolongation of I/R-induced QT interval-related arrhythmia. This study aimed to investigate whether isosteviol could attenuate I/R-induced prolongation of the action potential duration (APD) along with inhibition of I Kr , and we aimed to clarify the electrophysiological mechanism of isosteviol to determine its cardioprotective effects in guinea pigs. We observed that the APD 90 were 298.5   ±   41.6   ms in control, 528.6   ±   56.7   ms during I/R, and reduced to 327.8   ±   40.5   ms after 10   μmol/L of isosteviol treatment. The I Kr currents were 1.44   ±   0.06 pA·pF −   1 in the control group, 0.50   ±   0.07   pA·pF −   1 during I/R, and recovered to 1.20   ±   0.12   pA·pF −   1 after 10   μmol/L of isoteviol treatment. Moreover, isosteviol reduced the over-production of reactive oxygen species (ROS) during I/R. Importantly, isosteviol does not affect the I Kr and human ether-a-go-go-related gene currents of normal cardiomyocytes. It attenuated the I/R-induced inhibition of I Kr due to reduced over-production of ROS. Furthermore, isosteviol is safe and has no cardiotoxicity, and it might be beneficial for coronary reperfusion therapy.