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 beta-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 GABAB 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 GABAB receptors activate a K-channel that is blocked by tolbutamide.