Ischemic tolerance conferred to cultured rat neurons by heat shock is not mediated by opening of adenosine triphosphate-sensitive potassium channels

The effect of sublethal heat shock on the capacity of neurons to resist sub sequent ischemia-reperfusion-induced cell injury, was studied in a model of primary rat neuronal cultures, subjected to chemical ischemia. Exposure of the cultures to sublethal heat shock (42 degrees C; 20 min) resulted in el evation in cellular content of heat shock protein (HSP)-70, at 4 h followin g the shock, and in acquisition of a 15 h 'time window of protection' again st ischemia-reperfusion insult, with maximum protection at 4 h. Presence in the culture medium of glibenclamide (2 mu M), a blocker of ATP sensitive p otassium (K-ATP) channels, did not abolish the acquisition of protection th roughout the entire duration of the acquired 'time window of protection'. T he results demonstrate that heat shock induces in neurons a protective mech anism against ischemia-reperfusion insult, probably associated with enhance d expression of HSPs, which does not depend on opening of K-ATP channels. I n this respect, the neuronal 'heat-shock mechanism' for the acquisition of ischemic tolerance differs from the neuronal 'adenosine mechanism' and prob ably also from the heart 'heat shock mechanism' for the acquisition of prot ection. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.