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© The Rockefeller University Press, 0022-1295/1999//415/ $5.00
Journal of General Physiology, Volume 114, Number 3, 1999


Original Article

Tuning the Voltage Dependence of Tetraethylammonium Block with Permeant Ions in an Inward-Rectifier K+ Channel

Maria Spassovaa and Zhe Lua

a From the Department of Physiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104
University of Pennsylvania, Department of Physiology, D302A Richards Building, 3700 Hamilton Walk, Philadelphia, PA 19104-6085.Fax: 215-573-5851;

zhelu{at}mail.med.upenn.edu

To understand the role of permeating ions in determining blocking ion–induced rectification, we examined block of the ROMK1 inward-rectifier K+ channel by intracellular tetraethylammonium in the presence of various alkali metal ions in both the extra- and intracellular solutions. We found that the channel exhibits different degrees of rectification when different alkali metal ions (all at 100 mM) are present in the extra- and intracellular solution. A quantitative analysis shows that an external ion site in the ROMK1 pore binds various alkali metal ions (Na+, K+, Rb+, and Cs+) with different affinities, which can in turn be altered by the binding of different permeating ions at an internal site through a nonelectrostatic mechanism. Consequently, the external site is saturated to a different level under the various ionic conditions. Since rectification is determined by the movement of all energetically coupled ions in the transmembrane electrical field along the pore, different degrees of rectification are observed in various combinations of extra- and intracellular permeant ions. Furthermore, the external and internal ion-binding sites in the ROMK1 pore appear to have different ion selectivity: the external site selects strongly against the smaller Na+, but only modestly among the three larger ions, whereas the internal site interacts quite differently with the larger K+ and Rb+ ions.

Key Words: inward-rectifier K+ channel • rectification • ionic blocker • ion selectivity • tetraethylammonium


© 1999 The Rockefeller University Press


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