Referenced in: none

Automatically associated channels: Kir1.1 , Kir2.1 , Kir3.2 , Kir4.1 , Kir6.2

Title: Subunit-specific inhibition of inward-rectifier K+ channels by quinidine.

Authors: T Doi, B Fakler, J H Schultz, H Ehmke, U Brandle, H P Zenner, H Süssbrich, F Lang, J P Ruppersberg, A E Busch

Journal, date & volume: FEBS Lett., 1995 Nov 20 , 375, 193-6

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/7498497

Abstract
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' rectifier channel ROMK1 was only moderately inhibited. ROMK1(N171D)-IRK1C-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.