title: Acceleration of P/C-type inactivation in voltage-gated K(+) channels by methionine oxidation.
abstract: Oxidation of amino acid residues causes noticeable changes in gating of many ion channels. We found that P/C-type inactivation of Shaker potassium channels expressed in Xenopus oocytes is irreversibly accelerated by patch excision and that this effect was mimicked by application of the oxidant H(2)O(2), which is normally produced in cells by the dismutase action on the superoxide anion. The inactivation time course was also accelerated by high concentration of O(2). Substitution of a methionine residue located in the P-segment of the channel with a leucine largely eliminated the channel's sensitivity to patch excision, H(2)O(2), and high O(2). The results demonstrate that oxidation of methionine is an important regulator of P/C-type inactivation and that it may play a role in mediating the cellular responses to hypoxia/hyperoxia.
authors.affiliation: Department of Physiology, The University of Iowa, Iowa City, Iowa 52242 USA.
authors.forename: J
authors.initials: J
authors.lastname: Chen
authors.forename: V
authors.initials: V
authors.lastname: Avdonin
authors.forename: M A
authors.initials: MA
authors.lastname: Ciorba
authors.forename: S H
authors.initials: SH
authors.lastname: Heinemann
authors.forename: T
authors.initials: T
authors.lastname: Hoshi
mesh_terms: D000818:Animals; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D015640:Ion Channel Gating; D008564:Membrane Potentials; D008715:Methionine; D016254:Mutagenesis, Insertional; D009865:Oocytes / Q000502:physiology; D010084:Oxidation-Reduction; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D011994:Recombinant Proteins / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D051637:Shaker Superfamily of Potassium Channels; D014982:Xenopus laevis
chemical_list: D015221:Potassium Channels; D011994:Recombinant Proteins; D051637:Shaker Superfamily of Potassium Channels; D008715:Methionine; D006861:Hydrogen Peroxide