THE ROLE OF ATP-SENSITIVE POTASSIUM CHANNELS IN STRIATAL DOPAMINE RELEASE - AN IN-VIVO MICRODIALYSIS STUDY

We used in vivo brain microdialysis to investigate the role of adenosine triphosphate (ATP)-sensitive potassium (K-ATP) channels in dopamine (DA) release regulated by DA autoreceptors in the rat striatum. Local infusions of the K-ATP channel opener nicorandil (10(-5)-10(-3) M) into the striatum through the dialysis membrane produced dose-dependent decreases in extracellular concentrations of DA. Local application of the D-2 receptor antagonist (-)-sulpiride (SLP, 10(-5) M) or the K-ATP channel blocker quinine (QIN, 10(-3) M) produced significant increases in extracellular concentrations of DA. Nicorandil (10(-3) M) significantly blocked SLP (10(-5) M)- or QIN (10(-3) M)-induced increases in DA levels in the striatum. These results suggest that activation or inhibition of the K-ATP channel in the striatum causes decreases or increases, respectively, in endogenous DA release in vivo. Furthermore, SLP-induced increases in DA levels caused by blocking the tonic activation of DA autoreceptors are inhibited by the activation of K-ATP channels. These data suggest that striatal DA autoreceptors may inhibit DA release tonically by activating the K-ATP channel.