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 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 H₂O₂, 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 O₂. 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, H₂O₂, and high O₂. 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.