Micromolar concentrations of steroids and of aldosterone antagonists inhibit the outwardly rectifying chloride channel with different kinetics
Micromolar concentrations of steroids and of aldosterone antagonists inhibit the outwardly rectifying chloride channel with different kinetics
复制标题
微摩尔浓度的类固醇和醛固酮拮抗剂以不同的动力学抑制外向整流氯离子通道
DOI：
--
复制
发表时间：
2000
期刊：
影响因子：
--
通讯作者：
E. Frömter
中科院分区：
文献类型：
--
作者：
A. Rabe;E. Frömter
抽象的。我们用膜片钳技术分析了培养上皮细胞单个外向整流中电导(ORIC)Cl-通道在控制条件和不同抑制剂存在下的开放/关闭动力学。如先前在对照条件下切除的内/外斑块中观察到的，转换动力学由一个开放状态时间常数(τo≈30ms)和三个闭合状态时间常数(τc1≈0.2ms，τc2≈2ms和τc3≈60ms)表征。醛固酮、另外6种类固醇激素和2种醛固酮拮抗剂对通道开放概率的抑制作用呈依赖性，10µm o l/L作用强度依次为：氢化可的松、皮质酮、β雌二醇、可的松、醛固酮、睾酮、孕酮、坎利酮、螺内酯。虽然所有物质都降低了τo，但类固醇和醛固酮拮抗剂都不影响τc1、τc2或τc3，也不会以额外的时间常数诱导额外的转换。相反，类固醇增加了停留时间直方图中τc2的发生率，而醛固酮拮抗剂增加了τc3的发生率，两者都以浓度依赖的方式。这些观察可以用一个模型来解释，在该模型中，一个开放状态导致具有速率常数α，β和γ的三个闭合状态之一，并且β或γ分别在类固醇或醛固酮拮抗剂的影响下增加。也测试了含有未知分子结构的氯通道抑制剂的胞浆(Krick等人，PflügersArch 418：491,1991)，但结果不符合上述阻滞剂机制。这表明，甚至还有更多的通道抑制模式，并反对胞质氯通道抑制剂是类固醇。
Abstract. We used the patch-clamp technique to analyse the open/close kinetics of single, outwardly rectifying, intermediate-conductance (ORIC) Cl– channels from cultured epithelial cells under control conditions and in presence of different inhibitors. As observed previously in excised inside/out patches under control conditions, the switching kinetics were characterized by one open-state time constant (τo≈30 ms) and three closed-state time constants (τc1≈0.2 ms, τc2≈2 ms and τc3≈60 ms). Aldosterone, six further steroids and two aldosterone antagonists inhibited channel open probability (NPo) concentration dependently with the potency at 10 µmol/l increasing in the sequence: hydrocortisone, corticosterone, β-oestradiol, cortisone, aldosterone, testosterone, progesterone, canrenone, spironolactone. Although all substances decreased τo, neither the steroids nor the aldosterone antagonists affected τc1, τc2 or τc3 or induced additional transitions with additional time constants. Instead, the steroids increased the prevalence of τc2 in the dwell-time histograms and the aldosterone antagonists increased the prevalence of τc3, both in a concentration-dependent manner. These observations may be explained by a model in which one open state leads to one of three closed states with rate constants α, β and γ, and in which β or γ increase under the influence of steroids or aldosterone antagonists, respectively. Cytosol, which contains a Cl– channel inhibitor of unknown molecular structure, (Krick et al., Pflügers Arch 418:491, 1991) was also tested, but the results did not conform to the blocker mechanisms described above. This shows that there are even further modes of channel inhibition and argues against the cytosolic Cl– channel inhibitor being a steroid.
影响因子：
3.4
作者：
SIGWORTH, FJ;SINE, SM
通讯作者：
SINE, SM
三类化合物可阻断结肠 Cl 通道。
DOI：
10.1152/ajpcell.1991.261.1.c51
发表时间：
1991
期刊：
The American journal of physiology
影响因子：
--
作者：
Singh,AK;Afink,GB;Venglarik,CJ;Wang,RP;Bridges,RJ
通讯作者：
Bridges,RJ