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Acute Effect of Rosuvastatin on Left Ventricular Myocyte Calcium and Potassium Ion Channels

28434

Objective: Statins are widely used to lower plasma cholesterol levels due to their inhibitory effect on 3-hydoxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase activity which is central in cholesterol synthesis. Some pleiotropic properties of statins such as antiinflammatory, antioxidative, and antithrombotic as well as cardiovascular protective effects have been suggested. However, the direct actions of rosuvastatin which is a third generation synthetic statin on electrical activity of ventricular myocytes are still unknown. Materials and Methods: Ventricular myocytes isolated from rat hearts were used in this study. Action potentials (AP) were obtained with 1 Hz frequency stimuli using the current clamping mode of patch-clamp amplifier. Potassium and calcium currents were recorded using whole-cell configuration. Results: Rosuvastatin (1-10 μM) prolonged AP repolarization duration in a dose-dependent manner (n=15-16, respectively). For repolarizing currents rosuvastatin resulted in 14.57% and 17.75% (n=10) decrease in L-type calcium current (I_CaL) while the extent of decrease in transient-outward potassium current (I_to) was 8.28% and 27.59% (n=10) respectively. Steady-state K^+ current (I_ss) did not change significantly. Moreover, inactivation time constants of both currents were analyzed and rosuvastatin decreased the slow component of Ito currents significantly, whereas it didn’t influence the inactivation time constants of I_CaL. Conclusion: Although rosuvastatin reduced the amplitude of both Ito and I_CaL currents that play contradictory roles during repolarization of AP, the duration was significantly prolonged. It is likely that the suppression of Ito surmount the opposite effect of I_CaL reduction and prolongs the repolarization of AP.

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Rosuvastatin , action potential , Ca^2+ current , K^+ current , myocyte

Fırat University Medical Journal Of Health Sciences

166