Open AccessATP-Sensitive Potassium Channels Regulate In Vivo Dopamine Release in Rat Striatum
Author(s) -
Dawn Zhu,
James P. Sullivan,
Jorge D. Brioni
Publication year - 1999
Publication title -
japanese journal of pharmacology/japanese journal of pharmacology
Language(s) - Uncategorized
Resource type - Journals
eISSN - 1347-3506
pISSN - 0021-5198
DOI - 10.1254/jjp.79.59
Subject(s) - cromakalim , diazoxide , chemistry , striatum , dopamine , potassium channel , dopaminergic , medicine , extracellular , endocrinology , pharmacology , amphetamine , nigrostriatal pathway , substantia nigra , biology , biochemistry , agonist , receptor , insulin
ATP-sensitive K+ channels (K(ATP)) are distributed in a variety of tissues including smooth muscle, cardiac and skeletal muscle, pancreatic beta-cells and neurons. Since K(ATP) 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 K(ATP)-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 K(ATP) 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.