Effect of lactate on the synaptic potential, energy metabolism, calcium homeostasis and extracellular glutamate concentration in the dentate gyrus of the hippocampus from guinea-pig

Towards understanding the role of glycolysis on synaptic function, we examined the effect of lactate on synaptic potential, energy metabolism, Ca2+ homeostasis and extracellular glutamate in the dentate gyrus of guinea-pig hippocampus. Postsynaptic population spikes were recorded from the granule cell layer of the dentate gyrus in guinea-pig hippocampal slices after replacing glucose with lactate in the perfusion medium. Population spikes were not maintained and spontaneously recovered around 35 min after the replacement of glucose with lactate. However, ATP levels of the dentate gyrus remained unchanged while those during the glucose-free condition decreased to 73% of the initial levels at 60 min. Intracellular Ca2+ was measured with the calcium indicator dye fura-2 AM, and the population spike was recorded simultaneously. Ca2+ levels increased concomitantly with the early decay of synaptic potentials, and recovered partially with the spontaneous recovery of synaptic potentials. The time course of decay of population spikes and the increase of Ca2+ levels during lactate replacement were similar to those during glucose deprivation. Increase in Ca2+ levels during lactate replacement was completely blocked by the ryanodine receptor/calcium release channel antagonist dantrolene. Glutamate was released more significantly in the medium during lactate replacement than with normal Ringer solution, and less than that during glucose deprivation. Addition of the N-methyl-D-aspartate blocker, D-(-)-2-amino-5-phosphonovaleric acid, and the L-type calcium channel blocker, nimodipine, but not dantrolene blocked spontaneous recovery of population spikes. The results indicate that lactate can maintain energy levels in hippocampal slices, hut cannot maintain ion homeostasis in granule cells of the dentate gyrus. Glycolysis plays an important role in maintaining ion homeostasis, and activation of N-methyl- D-aspartate and L-type calcium channels is necessary for support of synaptic function by lactate utilization. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.