Rosuvastatin blocks hERG current and prolongs cardiac repolarization

Area of Science:

• Cardiovascular Pharmacology
• Molecular Cardiology
• Drug Safety

Background:

• Blocking the human ether-a-go-go related gene (hERG) potassium channel is linked to long QT syndrome (LQTS).
• Rosuvastatin, a statin, shares structural similarities with known hERG blockers.

Purpose of the Study:

• To investigate the effects of rosuvastatin on cardiac repolarization.
• To assess rosuvastatin's potential to block the hERG channel and induce LQTS.

Main Methods:

• In vitro patch clamp experiments on hERG-transfected cells.
• Ex vivo studies using isolated guinea pig hearts.
• In vivo assessment of QTc interval in conscious guinea pigs.

Main Results:

• Rosuvastatin demonstrated potent hERG channel blockade with an IC(50) of 195 nM.
• In isolated guinea pig hearts, rosuvastatin prolonged action potential duration.
• In vivo, rosuvastatin administration prolonged the corrected QT interval in guinea pigs.

Conclusions:

• Rosuvastatin blocks the hERG potassium current and prolongs cardiac repolarization.
• Transporter proteins (BCRP, MDR1, OATP2B1) influence hERG blockade by rosuvastatin.
• Genetic variations in these transporters may predispose certain patients to rosuvastatin-induced LQTS.