Are voltage-dependent ion channels involved in the endothelial cell control of vasomotor tone?
Are voltage-dependent ion channels involved in the endothelial cell control of vasomotor tone?
复制标题
DOI：
10.1152/ajpheart.01368.2006
复制
发表时间：
2007-09-01
影响因子：
4.8
通讯作者：
Duling, Brian R.
中科院分区：
文献类型：
--
作者：
Figueroa, Xavier F.;Chen, Chien-Chang;Duling, Brian R.
在微循环中，血管反应的纵向传导提供了在复杂网络中协调血管之间的流量分配的基本手段。电流沿着血管轴的传播可显示再生成分，这导致血管扩张信号传播超过许多毫米;再生反应的离子基础尚不清楚。我们研究了小鼠提睾肌小动脉对10 s局灶性电刺激（30 Hz，2 ms，30 V）的反应，以验证电压依赖性Na+（Na-v）和Ca 2+通道可能在微血管的长距离信号中被激活的假设。电刺激诱发的血管收缩的刺激和扩散，非递减进行扩张的网站。内皮损伤（气泡）阻断了血管舒张的传导，表明内皮受累。Nav通道阻断剂布比卡因也阻断传导，TTX使其减弱，Nav通道激活剂曲马定诱导内皮依赖性舒张。通过免疫细胞化学方法在提睾肌小动脉的内皮细胞中检测到Na（v）1.2、Na（v）1.6和Na（v）1.9亚型。这些发现是一致的参与导航频道进行响应。BAPTA缓冲内皮细胞Ca ~（2+）延迟并减少传导性扩张，这几乎被Ni ~（2+）、阿米洛利或α（1H）T型Ca ~（2+）（Ca（v）3.2）通道的缺失消除。阻断内皮型一氧化氮合酶或Ca ~（2+）激活的K ~+通道也可抑制传导性血管舒张。我们的研究结果表明，电诱导信号可以通过内皮细胞沿着血管轴沿着传播，并可以诱导Nav和Cav3.2通道的顺序激活。由此产生的Ca 2+内流激活内皮一氧化氮合酶和Ca 2+激活的K+通道，触发血管舒张。
In the microcirculation, longitudinal conduction of vasomotor responses provides an essential means of coordinating flow distribution among vessels in a complex network. Spread of current along the vessel axis can display a regenerative component, which leads to propagation of vasomotor signals over many millimeters; the ionic basis for the regenerative response is unknown. We examined the responses to 10 s of focal electrical stimulation (30 Hz, 2 ms, 30 V) of mouse cremaster arterioles to test the hypothesis that voltage-dependent Na+ (Na-v) and Ca2+ channels might be activated in long-distance signaling in microvessels. Electrical stimulation evoked a vasoconstriction at the site of stimulation and a spreading, nondecremental conducted dilation. Endothelial damage (air bubble) blocked conduction of the vasodilation, indicating an involvement of the endothelium. The Nav channel blocker bupivacaine also blocked conduction, and TTX attenuated it. The Nav channel activator veratridine induced an endothelium-dependent dilation. The Nav channel isoforms Na(v)1.2, Na(v)1.6, and Na(v)1.9 were detected in the endothelial cells of cremaster arterioles by immunocytochemistry. These findings are consistent with the involvement of Nav channels in the conducted response. BAPTA buffering of endothelial cell Ca2+ delayed and reduced the conducted dilation, which was almost eliminated by Ni2+, amiloride, or deletion of alpha(1H) T-type Ca2+ (Ca(v)3.2) channels. Blockade of endothelial nitric oxide synthase or Ca2+-activated K+ channels also inhibited the conducted vasodilation. Our findings indicate that an electrically induced signal can propagate along the vessel axis via the endothelium and can induce sequential activation of Nav and Cav3.2 channels. The resultant Ca2+ influx activates endothelial nitric oxide synthase and Ca2+-activated K+ channels, triggering vasodilation.