title: Modulation of gating of cloned rat and human K+ channels by micromolar Zn2+.
abstract: The actions of zinc ions on three species of K+ channels were studied using mouse fibroblasts stably transfected with a plasmid containing both the appropriate K+ channel gene and a steroid-inducible promotor. The channels studied were rKv1.1 and hKv1.5, delayed rectifiers cloned from rat and human tissue, respectively, and hKv1.4, an inactivating human K+ channel. Zn2+ shifted the activation curves for all three K+ currents in the depolarizing direction and also shifted the steady state inactivation curve for hKv1.4 in the depolarizing direction. The effect of Zn2+ was concentration dependent between 2 and 1000 microM. As a consequence of the modulation of gating, the activation kinetics of the K+ currents were slowed by Zn2+, an effect likely to delay repolarization of the neuronal action potential. The action of Zn2+ on these diverse K+ channels suggests the existence of a common Zn2+ binding domain, the occupation of which influences the voltage sensor. The resulting modulation of gating of hKv1.4 by Zn2+ may well be of physiological significance, in view of the localization of this channel in mossy fiber nerve terminals in the hippocampus, where Zn2+ is found in abundance.
authors.affiliation: Department of Anesthesia and Critical Care, University of Chicago, Illinois 60637.
authors.forename: N L
authors.initials: NL
authors.lastname: Harrison
authors.forename: H K
authors.initials: HK
authors.lastname: Radke
authors.forename: M M
authors.initials: MM
authors.lastname: Tamkun
authors.forename: D M
authors.initials: DM
authors.lastname: Lovinger
mesh_terms: D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D003001:Cloning, Molecular; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005347:Fibroblasts; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects*; D007700:Kinetics; D051379:Mice; D015221:Potassium Channels / Q000187:drug effects* / Q000235:genetics; D051381:Rats; D015032:Zinc / Q000494:pharmacology*
chemical_list: D015221:Potassium Channels; D015032:Zinc