FEBS Letters | |
Subunit‐specific inhibition of inward‐rectifier K+ channels by quinidine | |
Lang, F.1  Zenner, H.-P.3  Doi, T.3  Ruppersberg, J.P.3  Schultz, J.H.2  Ehmke, H.2  Busch, A.E.1  Brändle, U.3  Süßbrich, H.1  Fakler, B.3  | |
[1] Institute of Physiology, University of Tübingen, Gmelinstr. 5, 72076 Tübingen, Germany;Institute of Physiology, University of Heidelberg, Im Neuenheimer Feld, 69120 Heidelberg, Germany;Department of Sensory Biophysics, ENT-Hospital of the University of Tübingen, Röntgenweg 11, 72076 Tübingen, Germany | |
关键词: Quinidine; Inward rectifier K+ channel; pH; | |
DOI : 10.1016/0014-5793(95)01182-E | |
学科分类:生物化学/生物物理 | |
来源: John Wiley & Sons Ltd. | |
【 摘 要 】
Distinct inward-rectifier K+ channel subunits were expressed in Xenopus oocytes and tested for their sensitivity to the channel blocker quinidine. The ‘strong’ inward-rectifier K+ channel IRK1 was inhibited by quinidine with an EC50 of 0.7 mM, while the ‘weak’ reactifier channel ROMK1 was only moderately inhibited. ROMK1(N171D)-IRKIC-term chimeric channels, which carry both sites for strong rectification of IRK1 channels (the negatively charged D171 in the second transmembrane domain and the IRK1-C-terminus including E224), displayed strong rectification like IRK1, but showed weak sensitivity to quinidine-like ROMK1, suggesting independence of quinidine binding and rectification mechanisms. Moreover, BIR10 and BIR11, two strong rectifier subunits originally cloned from rat brain, exerted subunit-specific sensitivity to quinidine, being much higher for BIR11. Quinidine blockade of IRK1 was not voltage-dependent, but strongly dependent on the pH in the superfusate. These results strongly suggest a subunit-specific interaction of inward-rectifier K+ channels with neutral quinidine within membrane lipid bilayers.
【 授权许可】
Unknown
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