Department of Cardiology, the First Affiliated Hospital, China Medical University, Heping District, Shengyang, People's Republic of China.
Mol Cell Biochem. 2010 May;338(1-2):59-68. doi: 10.1007/s11010-009-0338-4. Epub 2009 Dec 1.
The large conductance Ca(2+)-activated K(+) (BK) channel, abundantly expressed in vascular smooth muscle cells, plays a critical role in controlling vascular tone. Activation of BK channels leads to membrane hyperpolarization and promotes vasorelaxation. BK channels are activated either by elevation of the intracellular Ca(2+) concentration or by membrane depolarization. It is also regulated by a diversity of vasodilators and vasoconstrictors. Interleukin-1beta (IL-1beta) is one of the cytokines that play important roles in the development and progression of a variety of cardiovascular diseases. The effects of IL-1beta on vascular reactivity are controversial, and little is known about the modulation of BK channel function by IL-1beta. In this study, we investigated how IL-1beta modulates BK channel function in cultured arterial smooth muscle cells (ASMCs), and examined the role of H(2)O(2) in the process. We demonstrated that IL-1beta had biphasic effects on BK channel function and membrane potential of ASMCs, that is both concentration and time dependent. IL-1beta increased BK channel-dependent K(+) current and hyperpolarized ASMCs when applied for 30 min. While long-term (24-48 h) treatment of IL-1beta resulted in decreased expression of alpha-subunit of BK channel, suppressed BK channel activity, decreased BK channel-dependent K(+) current and depolarization of the cells. H(2)O(2) scavenger catalase completely abolished the early effect of IL-1beta, while it only partly diminished the long-term effect of IL-1beta. These results may provide important molecular mechanisms for therapeutic strategies targeting BK channel in inflammation-related diseases.
大电导钙激活钾（BK）通道在血管平滑肌细胞中大量表达，在控制血管张力方面起着关键作用。BK 通道的激活导致细胞膜超极化，并促进血管舒张。BK 通道的激活要么是通过细胞内钙离子浓度的升高，要么是通过细胞膜去极化。它还受到多种血管扩张剂和血管收缩剂的调节。白细胞介素-1β（IL-1β）是在多种心血管疾病的发展和进展中起重要作用的细胞因子之一。IL-1β 对血管反应性的影响存在争议，并且对于 IL-1β 对 BK 通道功能的调节知之甚少。在这项研究中，我们研究了 IL-1β 如何调节培养的动脉平滑肌细胞（ASMCs）中的 BK 通道功能，并研究了 H₂O₂在该过程中的作用。我们证明，IL-1β对 ASMCs 的 BK 通道功能和膜电位具有双相作用，即具有浓度和时间依赖性。IL-1β 在应用 30 分钟时增加 BK 通道依赖性 K⁺电流并使 ASMC 超极化。然而，IL-1β 的长期（24-48 小时）处理导致 BK 通道α亚单位的表达减少，抑制 BK 通道活性，降低 BK 通道依赖性 K⁺电流并使细胞去极化。H₂O₂清除剂 Catalase 完全消除了 IL-1β 的早期作用，而仅部分消除了 IL-1β 的长期作用。这些结果可能为针对炎症相关疾病中 BK 通道的治疗策略提供重要的分子机制。
