Reversal of glibenclamide and voltage block of an epithelial KATP channel.
Reversal of glibenclamide and voltage block of an epithelial KATP channel.
复制标题
格列本脲的逆转和上皮 KATP 通道的电压阻断。
DOI：
10.1152/ajpcell.1996.271.4.c1122
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Schultz,SG
中科院分区：
文献类型：
--
作者：
Mayorga-Wark,O;Dubinsky,WP;Schultz,SG
K+通道存在于基底外侧膜囊泡分离自Necturus maculosa小肠细胞和重建成平面磷脂双层抑制MgATP和磺酰脲衍生物，如甲苯磺丁脲和格列本脲，当这些代理商被添加到解决方案洗澡通道的内口。此外，这些通道具有固有的“电压门”，并且当跨通道的电势差被定向为使得内部溶液相对于外部溶液为正电时被阻断。我们现在表明，增加渗透性离子的浓度，如K+或Rb+在外部溶液中逆转通道抑制所产生的50 μ M格列本脲的内部解决方案，也抑制固有的电压门控;这些影响并没有引起通过增加浓度的相对不渗透性离子，Na+或胆碱，在外部解决方案。此外，在不存在格列本脲的情况下增加外部溶液中的K+浓度抑制电压门控，并且在这些条件下，随后向内部溶液中加入格列本脲是无效的。这些结果与模型一致，其中电压门是一种开放通道阻滞剂，其作用通过升高相对渗透性阳离子的外部浓度直接逆转，格列本脲的作用是稳定通道的失活状态，可能通过疏水相互作用。
K+ channels present in basolateral membrane vesicles isolated from Necturus maculosa small intestinal cells and reconstituted into planar phospholipid bilayers are inhibited by MgATP and sulfonylurea derivatives, such as tolbutamide and glibenclamide, when these agents are added to the solution bathing the inner mouth of the channel. In addition, these channels possess an intrinsic "voltage gate" and are blocked when the electrical potential difference across the channel is oriented so that the inner solution is electrically positive with respect to the outer solution. We now show that increasing the concentration of permeant ions such as K+ or Rb+ in the outer solution reverses channel inhibition resulting from the addition of 50 microM glibenclamide to the inner solution and also inhibits intrinsic voltage gating; these effects are not elicited by increasing the concentrations of the relatively impermeant ions, Na+ or choline, in the outer solution. Furthermore, increasing the K+ concentration in the outer solution in the absence of glibenclamide inhibits voltage gating, and, under these conditions, the subsequent addition of glibenclamide to the inner solution is ineffective. These results are consistent with a model in which the voltage gate is an open-channel blocker whose action is directly reversed by elevating the external concentration of relatively permeant cations and where the action of glibenclamide is to stabilize the inactivated state of the channel, possibly through hydrophobic interactions.