BACKGROUND: Statins have shown pleiotrophic effects beyond cholesterol lowering. Statins have shown AF suppression effects. Atrial cardiomyocytes have a constitutively active acetylcholine-activated K+ current that is enhanced by atrial tachycardia. Acetylcholine activated K+ current (IKACh) is important for AF initiation and maintenance. Effects of statins on IKACh have not previously been evaluated.
METHODS AND RESULTS: IKACh current was recorded by nystatin-perforated patch-clamp technique, it was activated by acetylcholine (100 μM for 2 min). When atrial myocytes were pretreated lipophilic statins (simvastatin 10 μM for 10 min), and compared with a hydrophilic statin (pravastatin 10 μM for 10 min), we found that simvastatin, but not pravastatin significantly inhibited IKACh current. (p<0.05. Fig). Simvastatin-induced the IKACh inhibition were (10 μM, 5 μM, 3 μM, 1 μM) dose dependent. To investigate the mechanism of simvastatin-induced the IKACh inhibition, we evaluated mevalonate (MVA) 100 μM, geranylgeranyl pyrophosphate (GGPP) 10 μM, and farnesyl pyrophosphate (FPP) 10 μM on simvastatin induced IKACh current blocking effects. We found that MVA, GGPP, FPP did not recover simvastatin’s IKACh blocking effects. These results indicated that the simvastatin-induced the IKACh inhibition was unrelated to the MVA pathway. CONCLUSION: Lipophilic statin, simvastatin but not hydrophilic statin, pravastatin suppressed IKACh current. These results provide important background information for using lipophilic statin for treating AF patients.
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