ATP-sensitive potassium channels counteract anoxia in neurones of the substantia nigra

Summary The ATP-sensitive potassium channel (K_ATP channel) is a unique ionophore in that it appears to reflect cell metabolism. In the brain, the highest density of binding sites for the K_ATP channel is the substantia nigra. To evaluate the role of the K_ATP channel in this key brain area for motor control, we used exposure to cyanide to lower intracellular ATP and thereby mimic anoxia and ischemia. Treatment with cyanide caused the activation of a potassium current in a sub-population of nigral neurones with distinct pharmacological and electrophysiological properties. The response to cyanide was abolished by the sulphonylurea tolbutamide, a potent blocker of the K_ATP channel. These results suggest that in the substantia nigra, the K_ATP channel plays a pivotal role in normal mechanisms of neuronal homeostasis in response to anoxia and ischaemia. The significance of these findings for our understanding of the cellular mechanisms in Parkinsonian degeneration is discussed.