External TEA block of shaker K+ channels is coupled to the movement of K+ ions within the selectivity filter.
Recent molecular dynamic simulations and electrostatic calculations suggested that the external TEA binding site in K+ channels is outside the membrane electric field. However, it has been known for some time that external TEA block of Shaker K+ channels is voltage dependent. To reconcile these two results, we reexamined the voltage dependence of block of Shaker K+ channels by external TEA. We found that the voltage dependence of TEA block all but disappeared in solutions in which K+ ions were replaced by Rb+. These and other results with various concentrations of internal K+ and Rb+ ions suggest that the external TEA binding site is not within the membrane electric field and that the voltage dependence of TEA block in K+ solutions arises through a coupling with the movement of K+ ions through part of the membrane electric field. Our results suggest that external TEA block is coupled to two opposing voltage-dependent movements of K+ ions in the pore: (a) an inward shift of the average position of ions in the selectivity filter equivalent to a single ion moving approximately 37% into the pore from the external surface; and (b) a movement of internal K+ ions into a vestibule binding site located approximately 13% into the membrane electric field measured from the internal surface. The minimal voltage dependence of external TEA block in Rb+ solutions results from a minimal occupancy of the vestibule site by Rb+ ions and because the energy profile of the selectivity filter favors a more inward distribution of Rb+ occupancy.
Thompson
Jill
J
Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, NY 14642, USA.
Begenisich
Ted
T
D000818:Animals; D001665:Binding Sites / Q000502:physiology; D001667:Binding, Competitive / Q000502:physiology; D004553:Electric Conductivity; D004563:Electrochemistry; D015640:Ion Channel Gating / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology*; D015221:Potassium Channels / Q000737:chemistry / Q000378:metabolism*; D012413:Rubidium / Q000378:metabolism; D051637:Shaker Superfamily of Potassium Channels; D019789:Tetraethylammonium / Q000378:metabolism*; D014982:Xenopus laevis
D015221:Potassium Channels; D051637:Shaker Superfamily of Potassium Channels; D019789:Tetraethylammonium; D012413:Rubidium