色满醇对缓慢激活的I(sK)通道的特异性阻断——对I(sK)通道在上皮细胞中作用的影响

Specific blockade of slowly activating I(sK) channels by chromanols -- impact on the role of I(sK) channels in epithelia.

作者信息

Suessbrich H, Bleich M, Ecke D, Rizzo M, Waldegger S, Lang F, Szabo I, Lang H J, Kunzelmann K, Greger R, Busch A E

机构信息

Institute of Physiology, Eberhard-Karls-Universität Tübingen, Germany.

出版信息

FEBS Lett. 1996 Nov 4;396(2-3):271-5. doi: 10.1016/0014-5793(96)01113-1.

DOI:10.1016/0014-5793(96)01113-1

PMID:8915001

Abstract

Chromanols, which were recently shown to inhibit cAMP-mediated Cl- secretion in colon crypts via a blockade of a cAMP-activated K+ conductance, were analyzed for their effects on distinct cloned K+ channels expressed in Xenopus oocytes. The lead chromanol 293B specifically inhibited I(sK) channels with an IC50 of 7 micromol/l without affecting the delayed rectifier Kv1.1 or the inward rectifier Kir2.1. Moreover, several other chromanols displayed the same rank order of potency for I(sK) inhibition as demonstrated in colon crypts. Finally, we tested the effects of the previously described I(sK) blocker azimilide on cAMP mediated Cl- secretion in rat colon crypts. Similar to 293B azimilide inhibited the forskolin induced Cl- secretion. These data suggest that I(sK) protein induced K+ conductances are the targets for the chromanol 293B and its analogues, and azimilide.

摘要

色满醇最近被证明可通过阻断环磷酸腺苷（cAMP）激活的钾离子电导来抑制结肠隐窝中cAMP介导的氯离子分泌，本研究分析了其对非洲爪蟾卵母细胞中表达的不同克隆钾离子通道的影响。先导色满醇293B特异性抑制I(sK)通道，半数抑制浓度（IC50）为7微摩尔/升，而不影响延迟整流钾通道Kv1.1或内向整流钾通道Kir2.1。此外，其他几种色满醇对I(sK)抑制作用的效力顺序与在结肠隐窝中观察到的相同。最后，我们测试了先前描述的I(sK)阻滞剂阿齐利特对大鼠结肠隐窝中cAMP介导的氯离子分泌的影响。与293B相似，阿齐利特抑制了福斯高林诱导的氯离子分泌。这些数据表明，I(sK)蛋白诱导的钾离子电导是色满醇293B及其类似物以及阿齐利特的作用靶点。