In vivo Identification and Quantitative Evaluation of Carrier-Mediated Transport of Lactate at the Cellular Level in the Striatum of Conscious, Freely Moving Rats

Abstract

Intracerebral dialysis has allowed the continuous, on-line measurement of lactate in the extracellular fluid (ECF) of conscious, freely moving rats. The rapid time response of the technique allows the direct determination of the time course of changes in lactate in ECF following externally imposed stimuli. The time course of lactate appearance in ECF was found to be considerably slower than that observed in tissue following electroconvulsive shock or during ischemia following cardiac arrest. The ECF data could be fit to an integrated Michaelis-Menten model that assumed reversible transport of lactate across the cell membrane. This transport was found to act only when energy supplies could maintain membrane integrity and function, since ECF levels of lactate failed to follow tissue levels after cardiac arrest when energy resources are depleted. The calculated rate of cellular lactate transport was two orders of magnitude faster than transport of lactate across the blood-brain barrier in the adult rat, and passive diffusion of lactate was not found to contribute significantly across either cell or blood-brain barriers. Probenecid, an inhibitor of acid transport, was able to block both the efflux of lactate from cell to ECF and the consequent reuptake of lactate by cells in the striatum of the rat following electroconvulsive shock or ischemia.