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Original Article

Dimension and Properties of the Inner Pore

Donglin Guo^a and Zhe Lu^a

^a Department of Physiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104
University of Pennsylvania, Department of Physiology, D302A, Richards Building, 3700 Hamilton Walk, Philadelphia, PA 19104.(215) 573-1940

zhelu{at}mail.med.upenn.edu

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 (k_on) of all examined QAs is significantly smaller than expected for a diffusion-limited process. Furthermore, a large (30-fold) drop in k_on 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 (9 Å) is comparable to that of a K⁺ ion with a single H₂O shell.

Key Words: ion selectivity • ion permeation • IRK1 • ROMK1 • TEA

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