Kinetics of inward-rectifier K+ channel block by quaternary alkylammonium ions. dimension and properties of the inner pore

The Journal of General Physiology
D Guo, Z Lu

Abstract

We examined block of two inward-rectifier K+ channels, IRK1 and ROMK1, by a series of intracellular symmetric quaternary alkylammonium ions (QAs) whose side chains contain one to five methylene groups. As shown previously, the ROMK1 channels bind larger QAs with higher affinity. In contrast, the IRK1 channels strongly select TEA over smaller or larger QAs. This remarkable difference in QA selectivity between the two channels results primarily from differing QA unbinding kinetics. The apparent rate constant for binding (kon) of all examined QAs is significantly smaller than expected for a diffusion-limited process. Furthermore, a large ( approximately 30-fold) drop in kon occurs when the number of methylene groups in QAs increases from three to four. These observations argue that between the intracellular solution and the QA-binding locus, there exists a constricted pathway, whose dimension ( approximately 9 A) is comparable to that of a K+ ion with a single H2O shell.

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Citations

Dec 25, 2012·Nature Structural & Molecular Biology·David J PossonCrina M Nimigean
Jan 25, 2008·Proceedings of the National Academy of Sciences of the United States of America·Aldo A Rodríguez-MenchacaJosé A Sánchez-Chapula
Mar 19, 2003·The Journal of General Physiology·Donglin GuoZhe Lu
Jun 27, 2002·The Journal of General Physiology·Shinghua Ding, Richard Horn
Oct 3, 2002·The Journal of General Physiology·Donglin Guo, Zhe Lu
Jun 16, 2004·The Journal of General Physiology·Weiyan Li, Richard W Aldrich
Sep 29, 2004·The Journal of General Physiology·Umberto BanderaliRémy Sauvé
Mar 30, 2005·The Journal of General Physiology·Hyeon-Gyu Shin, Zhe Lu
Jul 27, 2005·The Journal of General Physiology·Hyeon-Gyu ShinZhe Lu
Apr 12, 2006·The Journal of General Physiology·Harley T KurataColin G Nichols
Oct 29, 2008·The Journal of General Physiology·Andrés Jara-OsegueraLeón D Islas
Mar 1, 2012·The Journal of General Physiology·Jill Thompson, Ted Begenisich
Feb 24, 2004·Annual Review of Physiology·Zhe Lu
Apr 1, 2003·The Journal of Physiology·Jill Thompson, Ted Begenisich
Mar 6, 2019·Nature Chemical Biology·Shizhen WangColin G Nichols
Sep 24, 2015·Nature Communications·David J PossonCrina M Nimigean
Sep 14, 2012·Biochemistry·Natalie SmithersJ Malcolm East

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Methods Mentioned

BETA
chemical modification

Software Mentioned

pClamp6

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