Antidiabetic Sulphonylureas Stimulate Acetylcholine Release from Striatal Cholinergic Interneurones Through Inhibition of KATP Channel Activity

Abstract: The sulphonylureas tolbutamide and glibenclamide were shown to stimulate acetylcholine release from rat striatal slices. To determine the mechanism of this effect, whole-cell patch-clamp recordings were made from large neurones within the striatum that displayed morphological, electrophysiological, and pharmacological characteristics typical of cholinergic interneurones. Dialysis of these neurones with a pipette solution containing low concentrations of ATP produced a gradual hyperpolarisation that could be reversed by bath application of the sulphonylureas. In voltage-clamp studies, these compounds were shown to act through the inhibition of a potassium conductance. It is concluded that cholinergic interneurones within the rat striatum express sulphonylurea-sensitive ATP-sensitive potassium channel activity. These channels are probably cytoprotective and may prove to be novel sites of therapeutic modulation.