首页> 外文期刊>American Journal of Physiology >ATP masks stretch activation of epithelial sodium channels in A6 distal nephron cells.
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ATP masks stretch activation of epithelial sodium channels in A6 distal nephron cells.

机译:ATP掩盖了A6远端肾细胞中上皮钠通道的拉伸活化。

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The mechanosensitivity of the epithelial sodium channel (ENaC) is controversial. Using cell-attached patch-clamp techniques, we found that mechanical stretch stimulated ENaC in A6 distal nephron cells in only three of nine cell-attached patches. However, stretch consistently activated ENaC after apical ATP was scavenged with apical hexokinase plus glucose or after P(2) receptors in the patch were blocked. The mean open probability (P(o)) of ENaC was increased from 0.31 +/- 0.04 to 0.61 +/- 0.06 (P < 0.001; n = 9) when patch pipettes contained hexokinase and glucose, or from 0.24 +/- 0.05 to 0.55 +/- 0.11 (P < 0.01; n = 7) when patch pipettes contained suramin, respectively. A poorly hydrolyzable ATP analog, ATPgammaS, in the patch pipettes inhibited ENaC, reducing the P(o) from 0.41 +/- 0.06 to 0.19 +/- 0.05 (P < 0.01; n = 8). Pretreatment of A6 cells with the phospholipase C (PLC) inhibitor U-73122 abolished the effect of ATP on ENaC activity. These data together suggest that ATP, acting through a PLC-dependent purinergic pathway, masks stretch-induced ENaC activation.
机译:上皮钠通道(ENaC)的机械敏感性是有争议的。使用细胞附着的膜片钳技术,我们发现机械拉伸刺激了九个细胞附着的膜片中的三个中的A6远端肾单位中的ENaC。但是,用根己糖激酶加葡萄糖清除了ATP后,或者阻滞了斑块中的P(2)受体后,拉伸始终激活ENaC。当贴片移液器中含有己糖激酶和葡萄糖时,ENaC的平均打开概率(P(o))从0.31 +/- 0.04增加到0.61 +/- 0.06(P <0.001; n = 9),或者从0.24 +/- 0.05增加当贴片移液器中分别含有苏拉明时,浓度应降至0.55 +/- 0.11(P <0.01; n = 7)。贴片移液器中水解性差的ATP类似物ATPgammaS抑制ENaC,将P(o)从0.41 +/- 0.06降低到0.19 +/- 0.05(P <0.01; n = 8)。用磷脂酶C(PLC)抑制剂U-73122预处理A6细胞消除了ATP对ENaC活性的影响。这些数据共同表明,ATP通过PLC依赖的嘌呤能途径起作用,掩盖了拉伸诱导的ENaC激活。

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