Subunit‐specific inhibition of inward‐rectifier K+ channels by quinidine

FEBS Letters

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)-IRKI_C-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