Biochimica et Biophysica Acta - Biomembranes
Biochimica et Biophysica Acta - Biomembranes
5 years ago

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

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 (IKr) 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 IKr, and we aimed to clarify the electrophysiological mechanism of isosteviol to determine its cardioprotective effects in guinea pigs. We observed that the APD90 were 298.5±41.6ms in control, 528.6±56.7ms during I/R, and reduced to 327.8±40.5ms after 10μmol/L of isosteviol treatment. The IKr currents were 1.44±0.06 pA·pF−1in the control group, 0.50±0.07pA·pF−1during I/R, and recovered to 1.20±0.12pA·pF−1after 10μmol/L of isoteviol treatment. Moreover, isosteviol reduced the over-production of reactive oxygen species (ROS) during I/R. Importantly, isosteviol does not affect the IKr and human ether-a-go-go-related gene currents of normal cardiomyocytes. It attenuated the I/R-induced inhibition of IKr due to reduced over-production of ROS. Furthermore, isosteviol is safe and has no cardiotoxicity, and it might be beneficial for coronary reperfusion therapy.

Publisher URL: www.sciencedirect.com/science

DOI: S0005273617302778

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