Neuroprotection by ATP-dependent potassium channels in rat neocortical brain slices during hypoxia

Morphological changes induced by 30 min of hypoxia (incubation in medium saturated with 95% N-2-5% CO2 instead of the normal 95% O-2-5% CO2) were investigated in neurons (layers II/III of the parietal cortex) of rat neocortical brain slices. The cells were identified as intact, reversibly or irreversibly injured. As expected, hypoxia decreased the number of intact cells and increased the number of irreversibly injured cells. Pretreatment of slices with diazoxide (300 mu M), an agonist of ATP-dependent potassium (K-ATP) channels completely prevented the morphological damage induced by hypoxia, whereas tolbutamide (300 mu M), an antagonist of K-ATP channels, was ineffective when given alone. However, tolbutamide (300 mu M) co-applied with diazoxide (300 mu M), partly reversed the neuroprotective effect of this agonist during hypoxia. In conclusion, K-ATP channels appear to be present on neocortical neurons and their opening counteracts hypoxia-induced cell injury. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.