Dawn Xiao-Dong Zhu, James P. Sullivan and Jorge D. Brioni
Neurological and Urological Diseases Research, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064, USA
Abstract: ATP-sensitive K+ channels (KATP) are distributed in a variety of tissues including smooth muscle, cardiac and skeletal muscle, pancreatic, beta-cells and neurons. Since KATP channels are present in the nigrostriatal dopamine (DA) pathway, the effect of potassium-channel modulators on the release of DA in the striatum of conscious, freely-moving rats was investigated. The extracellular concentration of DA was significantly decreased by the KATP-channel opener (-)-cromakalim but not by diazoxide. (-)-Cromakalim was effective at 100 and 1000 microM concentrations, and the maximum decrease was 54% below baseline. d-Amphetamine significantly increased extracellular DA levels at the doses of 0.75 and 1.5 mg/kg, s.c. with a 770% maximum increase. (-)-Cromakalim had no effect on d-amphetamine-induced DA release, while glyburide, a KATP blocker, significantly potentiated the effects of a low dose of d-amphetamine. These data indicate that K+ channels present in the nigrostriatal dopaminergic terminals modulate basal release as well as evoked release of DA.
Keywords: Microdialysis, Dopamine, Amphetamine, Cromakalim, Glyburide