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External TEA Block of Shaker K+ Channels Is Coupled to the Movement of K+ Ions within the Selectivity Filter
Address correspondence to Ted Begenisich, Department of Pharmacology and Physiology, Box 711, University of Rochester Medical Center, Rochester, NY 14642. Fax: (585) 273-2652; email: ted_begenisich{at}URMC.rochester.edu
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
37% into the pore from the external surface; and (b) a movement of internal K+ ions into a vestibule binding site located 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.
Key Words: K+ channels • ion permeation • tetraethylammonium • rubidium
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