Potassium chloride depolarization enhances MPP +-induced hydroxyl radical generation in the rat striatum

Abstract

We determined that extracellular potassium ion concentration, [K +] o-induced depolarization, enhances 1-methyl-4-phenylpyridinium ion (MPP +)-induced hydroxyl radical (⋅OH) generation in the rat striatum. Rats were anesthetized, and sodium salicylate in Ringer's solution (0.5 nmol/μl/min) was infused through a microdialysis probe to detect the generation of ⋅OH as reflected by the non-enzymatic formation of 2,3-dihydroxybenzoic acid (DHBA) in the striatum. Induction of high concentration KCl (70 mM) drastically increased formation of ⋅OH trapped as DHBA by the action of MPP +. When dopamine (DA) was administered to the high KCl-treated animals, a marked elevation of DHBA was observed, compared with MPP +-only-treated animals, that showed a positive linear correlation between DA and ⋅OH formation trapped as DHBA ( R 2=0.979) in the dialysate. When corresponding experiments were performed with iron (II), the same results were obtained: a positive linear correlation between the release of iron (II) and DHBA ( R 2=0.988) in the dialysate. These results suggest that [K +] o-induced depolarization enhances the formation of ⋅OH products of efflux/oxidation due to MPP +.