MODULATION OF POTASSIUM CHANNEL FUNCTION BY METHIONINE OXIDATION AND REDUCTION

Oxidation of amino acid residues in proteins can be caused by a variet y of oxidizing agents normally produced by cells. The oxidation of met hionine in proteins to methionine sulfoxide is implicated in aging as well as in pathological conditions, and it is a reversible reaction me diated by a ubiquitous enzyme, peptide methionine sulfoxide reductase. The reversibility of methionine oxidation suggests that it could act as a cellular regulatory mechanism although no such in vivo activity h as been demonstrated. We show here that oxidation of a methionine resi due in a voltage-dependent potassium channel modulates its inactivatio n. When this methionine residue is oxidized to methionine sulfoxide, t he inactivation is disrupted, and it is reversed by coexpression with peptide methionine sulfoxide reductase. The results suggest that oxida tion and reduction of methionine could play a dynamic role in the cell ular signal transduction process in a variety of systems.