IL-1β modulate the Ca 2+ -activated big-conductance K channels (BK) via reactive oxygen species in cultured rat aorta smooth muscle cells

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-1β (IL-1β) is one of the cytokines that play important roles in the development and progression of a variety of cardiovascular diseases. The effects of IL-1β on vascular reactivity are controversial, and little is known about the modulation of BK channel function by IL-1β. In this study, we investigated how IL-1β 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-1β had biphasic effects on BK channel function and membrane potential of ASMCs, that is both concentration and time dependent. IL-1β increased BK channel-dependent K + current and hyperpolarized ASMCs when applied for 30 min. While long-term (24–48 h) treatment of IL-1β resulted in decreased expression of α-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-1β, while it only partly diminished the long-term effect of IL-1β. These results may provide important molecular mechanisms for therapeutic strategies targeting BK channel in inflammation-related diseases.