Abstract

Statins are known to exert vasculopretective effects which are independent of their cholesterol lowering ability. The aims of this study were to investigate a possible effect of atorvastatin on Ca²⁺-activated K⁺ channels (BK) in cultured rat aorta smooth muscle cells (ASMCs) and to assess their contribution to interleukin-1β (IL-1β) induced changes of membrane potential and BK activity. The membrane potential was determined by the intensity of DiBAC4 (3) detected under confocal microscope. We found that atorvastatin hyperpolarized ASMCs in a concentration-dependent manner. 100 μmol atorvastatin activated BK channel directly which is determined by patch-clamp experiments. 12 h treatment of IL-1β resulted in decreased BK channel activity and depolarization of the cells, while atorvastatin or hydrogen dioxide (H₂O₂) scavenger catalase completely abolished the effects. There was no synergistic effect when catalase and atorvastatin were applied together. Furthermore, perfusion with atorvastatin resulted in a similar pattern of BK activation with hyperpolarization of ASMCs treated with IL-1β, which have significant differences statistically in comparison with saline group. Our results provide a potential important molecular mechanism of non-lipid-lowering effects of the atorvastatin by modulating BK channel.

Key words: Atorvastatin, interleukin-1β (IL-1β), hydrogen dioxide, smooth muscle cells, K⁺ channels (BK) channel.