Tolbutamide reverses membrane hyperpolarisation induced by activation of D2 receptors and GABAB receptors in isolated substantia nigra neurones

A high density of binding sites for sulphonylureas is found in the substantia nigra. These binding sites may be linked to ATP-regulated K-channels (K-ATP channels) as sulphonylureas selectively inhibit these channels in pancreatic ß-cells. We have studied the effect of the sulphonylurea tolbutamide on the electrical properties of freshly isolated neurones from guinea-pig substantia nigra, using the perforated patch technique. In spontaneously firing cells, both the D₂ agonist quinpirole and the GABA_B agonist baclofen abolished firing, hyperpolarised the cell and increased the whole-cell conductance. Tolbutamide reversed all three effects, but was without effect in the absence of quinpirole or baclofen. We suggest that D₂ and GABA_B receptors activate a K-channel that is blocked by tolbutamide.