ACTIVATION OF ATP-SENSITIVE POTASSIUM CHANNELS DECREASES NEURONAL INJURY CAUSED BY CHEMICAL HYPOXIA

Cerebral ischemia is known to induce endogenous adaptive mechanisms su ch as the activation of ATP-sensitive potassium channels that can prev ent or delay neuronal injury. This process can be therapeutically mimi cked by treatment with potassium channel openers. Primary neuronal cel l cultures were derived from embryonic chick telencephalon and were ex posed to chemical hypoxia (1 mM cyanide) or excitotoxic injury (1 mM L -glutamate). While treatments with the potassium channel openers bimak alim (1-10 mu M) and EMD 57283 (0.1-10 mu M) were clearly able to main tain neuronal viability after chemical hypoxia, similar concentrations of the drugs had negligible effects on glutamate-induced neurotoxicit y. In contrast, both types of neuronal injury were sensitive to the pr otective action of the glutamate receptor antagonist dizocilpine (MK-8 01; 0.1-1 mu M). The neuroprotective effect of bimakalim against chemi cally induced hypoxic injury was reversed by tolbutamide (1 mu M), an ATP-sensitive potassium channel blocker. These experiments demonstrate neuroprotective effects of potassium channel openers that could be re lated to inhibition of neurotransmitter release. (C) 1997 Elsevier Sci ence B.V.