PDF(Pubmed)
Abstract：
Cooling causes cutaneous dilatation to restrain cold-induced constriction and prevent tissue injury. Cooling increases communication through myoendothelial gap junctions (MEGJs), thereby increasing endothelium-derived hyperpolarization (EDH)-type dilatation. EDH is initiated by calcium-activated potassium channels (KCa ) activated by endothelial stimuli or muscle-derived mediators traversing MEGJs (myoendothelial feedback). The goal of this study was to determine the individual roles of KCa with small (SK3) and intermediate (IK1) conductance in cooling-induced dilatation. Vasomotor responses of mice isolated cutaneous tail arteries were analyzed by pressure myography at 37°C and 28°C. Cooling increased acetylcholine-induced EDH-type dilatation during inhibition of NO and prostacyclin production. IK1 inhibition did not affect dilatations to acetylcholine, whereas SK3 inhibition inhibited dilatation at both temperatures. Cooling uncovered myoendothelial feedback to inhibit constrictions in U46619. IK1 inhibition did not affect U46619 constrictions, whereas SK3 inhibition abolished the inhibitory effect of cooling without affecting U46619 constriction at 37°C. Immunoblots confirmed SK3 expression, which was localized (immunofluorescence) to holes in the internal elastic lamina consistent with myoendothelial projections. Immunoblots and Immunofluorescence did not detect IK1. Studies in non-cutaneous arteries have highlighted the predominant role of IK1 in EDH-type dilatation. Cutaneous arteries are distinctly reliant on SK3, which may enable EDH-type dilation to be amplified by cooling.
摘要：
冷却引起皮肤扩张以抑制冷引起的收缩并防止组织损伤。冷却增加通过肌内皮缝隙连接（MEGJ）的交流，从而增加内皮衍生的超极化（EDH）型扩张。EDH是由钙激活的钾通道（KCa）启动的，该钾通道由内皮刺激或穿过MEGJ（肌内皮反馈）的肌肉衍生介质激活。这项研究的目的是确定具有小（SK3）和中等（IK1）电导的KCa在冷却引起的扩张中的个体作用。在37°C和28°C下通过压力肌电图分析小鼠分离的皮肤尾动脉的血管舒缩反应。在抑制NO和前列环素产生期间，冷却增加了乙酰胆碱诱导的EDH型扩张。IK1抑制不影响向乙酰胆碱的扩张,而SK3抑制抑制扩张在两个温度。冷却未覆盖肌内皮反馈以抑制U46619中的收缩。IK1抑制不影响U46619收缩，而SK3抑制消除了冷却的抑制作用，而不影响U46619在37°C的收缩。免疫印迹证实SK3表达，将其定位（免疫荧光）到与肌内皮投影一致的内部弹性层的孔中。免疫印迹和免疫荧光没有检测到IK1。对非皮肤动脉的研究强调了IK1在EDH型扩张中的主要作用。皮肤动脉明显依赖于SK3，这可能使EDH型扩张通过冷却而放大。
