Subunit-specific inhibition of inward-rectifier K+ channels by quinidine
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 moder...
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| Hauptverfasser: | , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
November 20, 1995
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| In: |
FEBS letters
Year: 1995, Jahrgang: 375, Heft: 3, Pages: 193-196 |
| ISSN: | 1873-3468 |
| DOI: | 10.1016/0014-5793(95)01182-E |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/0014-5793(95)01182-E Verlag, lizenzpflichtig, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1016/0014-5793%2895%2901182-E |
| Verfasserangaben: | T. Doi, B. Fakler, J.-H. Schultz, H. Ehmke, U. Brändle, H.-P. Zenner, H. Süßbrich, F. Lang, J.P. Ruppersberg, A.E. Busch |
MARC
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| 520 | |a 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. | ||
| 650 | 4 | |a Inward rectifier K+ channel | |
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| 700 | 1 | |a Busch, A.E. |e VerfasserIn |4 aut | |
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