Specific blockade of slowly activating IsK channels by chromanols — impact on the role of IsK channels in epithelia

FEBS Letters

Lang, F.¹  Ecke, D.³  Kunzelmann, K.³  Rizzo, M.³  Szabo, I.²  Bleich, M.³  Busch, A.E.²  Lang, H.-J.²  Suessbrich, H.²  Greger, R.³  Waldegger, S.² 

[1] Hoechst AG, D-65926 Frankfurt/Main, Germany;Institute of Physiology, Eberhard-Karls-Universität Tübingen, Gmelinstr. 5, D-72076 Tübingen, Germany;Institute of Physiology, Albert-Ludwigs-Universität, Hermann-Herder-Str. 7, D-79104 Freiburg, Germany

关键词: K+ channel;    cAMP;    IsK;    Chromanol;    Cl− secretion;   

DOI  :  10.1016/0014-5793(96)01113-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 μmol/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.

【 授权许可】

Unknown