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

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/microl/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 (R2 = 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 (R2 = 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+.