Acceleration of P/C-type inactivation in voltage-gated K+ channels by methionine oxidation

Oxidation of amino acid residues causes noticeable changes in gating of man y ion channels. We found that P/C-type inactivation of Shaker potassium cha nnels expressed in Xenopus oocytes is irreversibly accelerated by patch exc ision and that this effect was mimicked by application of the oxidant H2O2, which is normally produced in cells by the dismutase action on the superox ide anion. The inactivation time course was also accelerated by high concen tration of O-2. Substitution of a methionine residue located in the P-segme nt of the channel with a leucine largely eliminated the channel's sensitivi ty to patch excision, H2O2, and high O-2. The results demonstrate that oxid ation 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/hype roxia.