The role of ATP-sensitive potassium channels in striatal dopamine release: an in vivo microdialysis study

Abstract

We used in vivo brain microdialysis to investigate the role of adenosine triphosphate (ATP)-sensitive potassium (KATP) channels in dopamine (DA) release regulated by DA autoreceptors in the rat striatum. Local infusions of the KATP 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 D2 receptor antagonist (-)-sulpiride (SLP, 10(-5) M) or the KATP 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 KATP 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 KATP channels. These data suggest that striatal DA autoreceptors may inhibit DA release tonically by activating the KATP channel.