Interaction between quaternary ammonium ions in the pore of potassium channels. Evidence against an electrostatic repulsion mechanism.
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.
Thompson
J
J
Department of Pharmacology and Physiology, University of Rochester Medical Center, New York 14642, USA.
Begenisich
T
T
D000818:Animals; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D001667:Binding, Competitive / Q000502:physiology; D004563:Electrochemistry; D005260:Female; D005703:Gallamine Triethiodide / Q000494:pharmacology; D017353:Gene Deletion; D015640:Ion Channel Gating / Q000187:drug effects* / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008958:Models, Molecular; D016296:Mutagenesis / Q000502:physiology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D009865:Oocytes / Q000502:physiology; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000493:pharmacokinetics; D015221:Potassium Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D012413:Rubidium / Q000494:pharmacology; D051637:Shaker Superfamily of Potassium Channels; D019789:Tetraethylammonium / Q000494:pharmacology*; D014982:Xenopus laevis
D018733:Nicotinic Antagonists; D015221:Potassium Channels; D051637:Shaker Superfamily of Potassium Channels; D019789:Tetraethylammonium; D012413:Rubidium; D005703:Gallamine Triethiodide; D011188:Potassium