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Changes in Repolarizing Currents in Mouse Cardiomyocytes Following Chronic Atorvastatin Exposure
I Dzhumaniiazova1, T S Filatova1, G F Zakyrjanova1,2
1Lomonosov Moscow State University, Moscow, Russia.
Abstract:
Although statins are among the most frequently prescribed drugs worldwide, their effect on the electrical activity of the heart, especially under chronic exposure, is poorly studied. We analyzed changes in the main repolarizing potassium currents in ventricular cardiomyocytes isolated from mice under chronic atorvastatin exposure. The mice received atorvastatin in drinking water at a dose of 10 mg/kg for 1 month. The whole-cell patch-clamp measurements showed an increase in the ultrarapid delayed rectifier potassium current IKur in the experimental group of mice (by ~40% in comparison with the control), with no changes in the transient outward potassium current Ito and the inward rectifier potassium current IK1. No differences in the action potential configuration were revealed, which suggests possible changes in depolarizing currents under the influence of atorvastatin.
Insights
Chronic atorvastatin use in mice increased a key potassium current (IKur) in heart cells by 40%. This finding suggests potential impacts on cardiac electrical activity, warranting further investigation into statin drug effects.
Area of Science:
- Cardiology
- Pharmacology
- Electrophysiology
Background:
- Statins are widely prescribed globally, yet their chronic effects on cardiac electrical activity remain under-investigated.
- Understanding how statins influence heart cell electrophysiology is crucial for patient safety and therapeutic optimization.
Purpose of the Study:
- To investigate the impact of chronic atorvastatin exposure on key repolarizing potassium currents in ventricular cardiomyocytes.
- To determine if atorvastatin alters the ultrarapid delayed rectifier potassium current (IKur), transient outward potassium current (Ito), or inward rectifier potassium current (IK1).
Main Methods:
- Ventricular cardiomyocytes were isolated from mice subjected to chronic atorvastatin administration (10 mg/kg/day for 1 month).
- Whole-cell patch-clamp technique was employed to measure ion channel currents.
Main Results:
- A significant increase of approximately 40% in the ultrarapid delayed rectifier potassium current (IKur) was observed in atorvastatin-treated mice compared to controls.
- No significant changes were detected in the transient outward potassium current (Ito) or the inward rectifier potassium current (IK1).
- Action potential configuration remained unchanged, suggesting compensatory mechanisms or effects on other ion currents.
Conclusions:
- Chronic atorvastatin exposure selectively enhances the IKur in mouse ventricular cardiomyocytes.
- The observed changes in IKur, despite unaltered action potential morphology, indicate potential complex electrophysiological modulations by statins.
- Further research is needed to explore the effects of atorvastatin on depolarizing currents and the overall clinical implications.
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