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