Modulation of gating of cloned rat and human K+ channels by micromolar Zn2+.
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.
Harrison
N L
NL
Department of Anesthesia and Critical Care, University of Chicago, Illinois 60637.
Radke
H K
HK
Tamkun
M M
MM
Lovinger
D M
DM
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*
D015221:Potassium Channels; D015032:Zinc