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Original Article

Evidence against an Electrostatic Repulsion Mechanism

Jill Thompson^a and Ted Begenisich^a

^a Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, New York 14642
Department of Pharmacology and Physiology Box 711, University of Rochester Medical Center, Rochester, NY 14642.716-244-9283

ted_begenisich{at}urmc.rochester.edu

We have examined the interaction between internal and external ions in the pore of potassium channels. We found that external tetraethylammonium was able to antagonize block of Shaker channels by internal TEA when the external and internal solutions contained K⁺ ions. This antagonism was absent in solutions with Rb⁺ as the only permeant ion. An externally applied trivalent TEA analogue, gallamine, was less effective than the monovalent TEA in inhibiting block by internal TEA. In addition, block by external TEA was little affected by changes in the concentration of internal K⁺ ions, but was increased by the presence of internal Na⁺ ions in the pore. These results demonstrate that external and internal TEA ions, likely located at opposite ends of the pore selectivity filter, do not experience a mutual electrostatic repulsion. We found that these results can be simulated by a simple 4-barrier-3-site permeation model in which ions compete for available binding sites without long-range electrostatic interactions.

Key Words: ion channels • voltage-clamp • tetraethyl ammonium • gallamine • ion permeation

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