MODULATION OF GABA TRANSMISSION BY DIAZOXIDE AND CROMAKALIM IN THE GLOBUS-PALLIDUS - IMPLICATIONS FOR THE TREATMENT OF PARKINSONS-DISEASE

An ATP-sensitive potassium channel (K-ATP) is known to modulate insuli n release from pancreatic beta cells. It has been proposed that potass ium channels related to K-ATP in the nervous system might similarly mo dulate neurotransmitter release. We have therefore investigated the ef fects of K-ATP opening agents on GABA release in the globus pallidus. Diazoxide and cromakalim decreased the K+-evoked release of [H-3] GABA from pallidal slices. The maximum inhibition observed for diazoxide ( 59%) and cromakalim (66%) was achieved at a concentration of 100 mu M. The effects of both cromakalim and diazoxide were significantly antag onized by the concurrent application of the sulfonylurea glibenclamide (100 mu M). Intrapallidal injections of diazoxide in the reserpine-tr eated rat model of Parkinson's disease reduced akinesia in a dose-depe ndent manner. These data suggest that manipulation of neuronal potassi um channels with pharmacological properties similar to K-ATP may prove useful in the treatment of Parkinson's disease. (C) 1996 Academic Pre ss, Inc.