Tuning electrical conduction along endothelial tubes of resistance arteries through Ca(2+)-activated K(+) channels.
Tuning electrical conduction along endothelial tubes of resistance arteries through Ca(2+)-activated K(+) channels.
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DOI：
10.1161/circresaha.111.262592
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发表时间：
2012-05-11
影响因子：
20.1
通讯作者：
Segal SS
中科院分区：
文献类型：
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作者：
Behringer EJ;Segal SS
通过阻力血管内皮细胞间缝隙连接通道的电传导是血流控制不可或缺的部分。中小电导钙激活钾通道(SKCa/IKCa)启动内皮细胞内的电信号，但目前尚不清楚SKCa/IKCa激活是否会改变内皮细胞的信号传递。我们验证了SKCa/IKCa活性调节阻力血管内皮细胞电传导的假说。用双细胞内微电极对新鲜分离的小鼠骨骼肌腹上动脉内皮细胞管(宽60μm，长1-3 mm，细胞长约35μm)进行了研究。在第1点注入电流(±0.1-3nA)，在第2点记录膜电位(Vm)(间隔距离=50-2000μm)。在维持细胞间染料转移的情况下，SKCa/IKCa激活(NS309，1μ摩尔/L)可使内皮细胞沿内皮细胞管壁的Vm减少≥50%，电长度常数(λ)由1380缩短至850μm(P<；0.05)。用乙酰胆碱或SKA-31激活SKCa/IKCa也降低了电传导。当60 mM[K+]o阻止超极化(>；30 mV)时，SKCa/IKCa的这种激活效应持续存在。反之，阻断SKCa/IKCa(apamin+查氏毒素)使细胞去极化约10 mV，并增强电传导(即Vm的改变)约30%(P<；0.05)。这些发现说明了SKCa/IKCa活性在调节阻力血管内皮细胞的电传导中的一个新作用，即通过改变膜电阻来调节信号的耗散。因此，电压不敏感的离子通道可以独立于缝隙连接通道来调节细胞间的电信号。
Electrical conduction through gap junction channels between endothelial cells of resistance vessels is integral to blood flow control. Small and intermediate-conductance Ca2+-activated K+ channels (SKCa/IKCa) initiate electrical signals in endothelial cells but it is unknown whether SKCa/IKCa activation alters signal transmission along the endothelium. We tested the hypothesis that SKCa/IKCa activity regulates electrical conduction along the endothelium of resistance vessels. Freshly isolated endothelial cell tubes (60 μm wide; 1–3mm long; cell length, ~35 μm) from mouse skeletal muscle feed (superior epigastric) arteries were studied using dual intracellular microelectrodes. Current was injected (±0.1–3 nA) at Site 1 while recording membrane potential (Vm) at Site 2 (separation distance = 50–2000 μm). SKCa/IKCa activation (NS309, 1 μmol/L) reduced the change in Vm along endothelial cell tubes by ≥50% and shortened the electrical length constant (λ) from 1380 to 850 μm (P<0.05) while intercellular dye transfer (propidium iodide) was maintained. Activating SKCa/IKCa with acetylcholine or SKA-31 also reduced electrical conduction. These effects of SKCa/IKCa activation persisted when hyperpolarization (>30 mV) was prevented with 60 mM [K+]o. Conversely, blocking SKCa/IKCa (apamin + charybdotoxin) depolarized cells by ~10 mV and enhanced electrical conduction (i.e., changes in Vm) by ~30% (P<0.05). These findings illustrate a novel role for SKCa/IKCa activity in tuning electrical conduction along the endothelium of resistance vessels by governing signal dissipation through changes in membrane resistance. Voltage-insensitive ion channels can thereby tune intercellular electrical signaling independent from gap junction channels.