IL-1beta 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-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.
Gao
Yuan
Y
Department of Cardiology, the First Affiliated Hospital, China Medical University, Heping District, Shengyang, People's Republic of China.
Yang
Ying
Y
Guan
Qigang
Q
Pang
Xuefeng
X
Zhang
Haishan
H
Zeng
Dingyin
D
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects; D002374:Catalase / Q000378:metabolism; D002478:Cells, Cultured; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000494:pharmacology*; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000235:genetics / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D016877:Oxidants / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*
D053583:Interleukin-1beta; D051036:Large-Conductance Calcium-Activated Potassium Channels; D016877:Oxidants; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D002374:Catalase