U-37883A potently inhibits dopamine-modulated K+ channels on rat striatal neurons.
U-37883A potently inhibits dopamine-modulated K+ channels on rat striatal neurons.
复制标题
U-37883A 有效抑制大鼠纹状体神经元上多巴胺调节的 K 通道。
DOI：
10.1016/s0014-2999(98)00371-9
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发表时间：
1998
影响因子：
5
通讯作者：
Freedman,JE
中科院分区：
文献类型：
--
作者：
Lin,YJ;Chen,X;Freedman,JE
用细胞贴附式膜片钳技术研究了大鼠尾壳核神经元上一个可被多巴胺D2受体激活、被磺酰脲类药物抑制的85 pS钾离子通道。该通道可被外部应用的U-37883 A（4-morpholinecarboximidine-N-1-adamantyl-N '-cyclohexyl hydrochloride）抑制，U-37883 A是一种血管ATP敏感性K+通道的阻滞剂，在约0.1 μM的浓度下具有半数最大效应。当U-37883 A从回填式贴片移液器应用于膜时，通道抑制以时间依赖性方式发生。抑制与分数开放时间的减少，但电压不敏感，并没有改变通道电导，这表明在一个网站上的通道门控的影响很大程度上不敏感的电场通道。U-37883 A抑制该通道的效力比磺酰脲类药物格列本脲强约50倍。这种相对效力与胰腺组织中发现的相反，表明U-37883 A是区分磺酰脲敏感性K+通道不同亚型的有用工具。
An 85 pS K+channel of rat caudate–putamen neurons, which is activated by dopamine D2receptors and inhibited by sulfonylurea drugs, was studied using cell-attached patch-clamp electrophysiology. This channel was inhibited by externally-applied U-37883A (4-morpholinecarboximidine-N-1-adamantyl-N′-cyclohexyl hydrochloride), a blocker of vascular ATP-sensitive K+channels, with a half-maximal effect at a concentration of approximately 0.1 μM. Channel inhibition occurred in a time-dependent fashion when U-37883A was applied to the membrane from a back-filled patch pipette. Inhibition was associated with a decrease in fractional open time, but was voltage-insensitive and did not alter channel conductance, suggesting an effect on channel gating at a site largely insensitive to the electrical field of the channel. U-37883A was about 50 times more potent at inhibiting this channel than was the sulfonylurea drug glibenclamide. This relative potency, opposite to that found in pancreatic tissue, indicates that U-37883A is a useful tool to distinguish amongst different subtypes of sulfonylurea-sensitive K+channels.