title: A common inhibitory binding site for zinc and odorants at the voltage-gated K(+) channel of rat olfactory receptor neurons.
abstract: This study compared the effects of zinc and odorants on the voltage-gated K(+) channel of rat olfactory neurons. Zinc reduced current magnitude, depolarized the voltage activation curve and slowed activation kinetics without affecting inactivation or deactivation kinetics. Zinc inhibition was potentiated by the NO compound, S-nitroso-cysteine. The pH- and diethylpyrocarbonate-dependence of zinc inhibition suggested that zinc acted by binding to histidine residues. Cysteine residues were eliminated as contributing to the zinc-binding site. The odorants, acetophenone and amyl acetate, also reduced current magnitude, depolarized the voltage activation curve and selectively slowed activation kinetics. Furthermore, the diethylpyrocarbonate- and pH-dependence of odorant inhibition implied that the odorants also bind to histidine residues. Zinc inhibitory potency was dramatically diminished in the presence of odorants, implying competition for a common binding site. These observations indicate that the odorants and zinc share a common inhibitory binding site on the external surface of the voltage-gated K(+) channel.
authors.affiliation: Department of Physiology and Pharmacology, University of Queensland, Brisbane, QLD, 4072, Australia.
authors.forename: B
authors.initials: B
authors.lastname: Seebungkert
authors.forename: J W
authors.initials: JW
authors.lastname: Lynch
mesh_terms: D002731:4-Chloromercuribenzenesulfonate / Q000494:pharmacology; D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D002248:Carbon Monoxide / Q000494:pharmacology; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D053138:Cyclohexenes; D003545:Cysteine / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D004047:Diethyl Pyrocarbonate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006639:Histidine / Q000187:drug effects / Q000378:metabolism; D000077222:Limonene; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008698:Mesylates / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000494:pharmacology; D018034:Olfactory Receptor Neurons / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D000439:Pentanols / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D018035:Receptors, Odorant / Q000187:drug effects / Q000378:metabolism*; D012903:Smell / Q000187:drug effects / Q000502:physiology*; D013439:Sulfhydryl Reagents / Q000494:pharmacology; D013729:Terpenes / Q000494:pharmacology; D015032:Zinc / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D000098:Acetophenones; D053138:Cyclohexenes; D008698:Mesylates; D000439:Pentanols; D015221:Potassium Channels; D018035:Receptors, Odorant; D013439:Sulfhydryl Reagents; D013729:Terpenes; C109154:(2-(trimethylammonium)ethyl)methanethiosulfonate; D009569:Nitric Oxide; D006639:Histidine; D002731:4-Chloromercuribenzenesulfonate; D002248:Carbon Monoxide; C005716:amyl acetate; D000077222:Limonene; D015032:Zinc; D003545:Cysteine; D004047:Diethyl Pyrocarbonate; D011188:Potassium