Simulation of aspects of ischemia in cell culture: changes in lactate compartmentation.

Aspects of hyperglycemic ischemia were simulated in cultures of astrocytes and of neurons by high glucose and dinitrophenol exposure. Lactate release increased almost sevenfold and it was found that astrocytes were responsible for 92% of the release. There was no significant increase in internal lactate content. Experiments involving loading of astrocytes with lactate at different external pH values showed that lactate accumulation was increased by an increased inward proton gradient. This inward transport of lactate probably consists of two transport components, a passive diffusion of its neutral form and transport via a recently described monocarboxylic acid carrier. It was found that lactate did not get trapped in astrocytes, despite the fact that loading of astrocytes with lactic acid by exposure to 30 mM lactic acid increased the membrane input resistance dramatically. We conclude that lactate is released as lactic acid from astrocytes and equilibrates quickly with all CNS compartments. Thus we argue against a role of lactate accumulation in cytotoxic swelling.