Rabe A, Disser J, Frömter E
Zentrum der Physiologie, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt, Germany.
Pflugers Arch. 1995 Mar;429(5):659-62. doi: 10.1007/BF00373986.
As long as the question of which channels are responsible for cAMP-mediated epithelial Cl- secretion remains unsolved, it is still important to search for specific inhibitors that might help to relate macroscopic to microscopic events. Following the report by Sheppard and Welsh (J Gen Physiol 100: 573, 1992) that glibenclamide inhibits whole-cell Cl- currents in genetically manipulated fibroblasts expressing the cystic fibrosis transmembrane conductance regulator (CFTR), we have studied the effect of glibenclamide on different types of Cl- channels of HT29 and T84 cells at the single-channel level. Our results confirm that micromolar concentrations of glibenclamide inhibit the linear, low-conductance Cl-channel, which appears to represent CFTR and show that the inhibition results from a typical flicker block. However, the same concentrations of glibenclamide inhibit also the outwardly rectifying intermediate conductance Cl- channel which, potentially, may contribute to transepithelial Cl- secretion.
只要负责环磷酸腺苷（cAMP）介导的上皮细胞氯离子（Cl⁻）分泌的通道问题尚未解决，寻找可能有助于将宏观事件与微观事件联系起来的特异性抑制剂仍然很重要。在谢泼德和威尔士（《普通生理学杂志》100: 573, 1992）报道格列本脲抑制表达囊性纤维化跨膜电导调节因子（CFTR）的基因操作成纤维细胞中的全细胞Cl⁻电流之后，我们在单通道水平研究了格列本脲对HT29和T84细胞不同类型Cl⁻通道的影响。我们的结果证实，微摩尔浓度的格列本脲抑制线性、低电导Cl⁻通道，该通道似乎代表CFTR，并表明这种抑制是由典型的闪烁阻断引起的。然而，相同浓度的格列本脲也抑制外向整流性中等电导Cl⁻通道，该通道可能有助于跨上皮Cl⁻分泌。
