title: Allosteric effects of permeating cations on gating currents during K+ channel deactivation.
abstract: K+ channel gating currents are usually measured in the absence of permeating ions, when a common feature of channel closing is a rising phase of off-gating current and slow subsequent decay. Current models of gating invoke a concerted rearrangement of subunits just before the open state to explain this very slow charge return from opening potentials. We have measured gating currents from the voltage-gated K+ channel, Kv1.5, highly overexpressed in human embryonic kidney cells. In the presence of permeating K+ or Cs+, we show, by comparison with data obtained in the absence of permeant ions, that there is a rapid return of charge after depolarizations. Measurement of off-gating currents on repolarization before and after K+ dialysis from cells allowed a comparison of off-gating current amplitudes and time course in the same cells. Parallel experiments utilizing the low permeability of Cs+ through Kv1.5 revealed similar rapid charge return during measurements of off-gating currents at ECs. Such effects could not be reproduced in a nonconducting mutant (W472F) of Kv1.5, in which, by definition, ion permeation was macroscopically absent. This preservation of a fast kinetic structure of off-gating currents on return from potentials at which channels open suggests an allosteric modulation by permeant cations. This may arise from a direct action on a slow step late in the activation pathway, or via a retardation in the rate of C-type inactivation. The activation energy barrier for K+ channel closing is reduced, which may be important during repetitive action potential spiking where ion channels characteristically undergo continuous cyclical activation and deactivation.
authors.affiliation: Department of Physiology, Botterell Hall, Queen's University, Kingston, Ontario K7L 3N6, Canada.
authors.forename: F S
authors.initials: FS
authors.lastname: Chen
authors.forename: D
authors.initials: D
authors.lastname: Steele
authors.forename: D
authors.initials: D
authors.lastname: Fedida
mesh_terms: D002412:Cations / Q000378:metabolism*; D002460:Cell Line; D002586:Cesium; D004558:Electric Stimulation; D004594:Electrophysiology; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology; D009154:Mutation; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*
chemical_list: D002412:Cations; D015221:Potassium Channels; D002586:Cesium