Our work has focused on the interrelationship between neurons and astroglial cells and on the role that this interrelationship plays in cerebral energy metabolism. When neurons are stimulated, they release both neurotransmitters and potassium into the extracellular fluid. One of the ways in which the action of the excitatory neurotransmitter, glutamate, is terminated is by a solium-dependent uptake into the nearby astroglial cells. The sodium influx associated with the entry of glutamate has been shown by Pellerin and Magistretti and by Takahashi to stimulate glycolysis and and thereby glucose utilization in the astroglial cells. The increase in extracellular potassium which follows neuronal stimulation does not increase glucose utilization but does produce a significant shift in pyruvate utilization from lactate formation to the anaplerotic reactions associated with CO-2 formation. Lactate production is decreased and the de novo synthesis of glutamate and glutamine derived from CO-2 fixation is markedly increased. These results suggest that the role of sodium is to regulate the rate at which glucose enters the astroglial glycolytic pathway and is converted to pyruvate, whereas the role of potassium is to regulate the distribution of this pyruvate between lactate formation and CO-2 fixation, that is, between a reacion which provides a source of energy for the surrounding neurons and one which has an anaplerotic or biosynthetic function. The work described above has been expanded to include stdies on the effect of the neuroactive drug, gamma-hydroxybutyrate (GHB) on the metabolism of glucose and lactate in both neurons and astroglia. The effect of GHB on both glycolytic and oxidative metabolism has been studied. Since transport of lactate and glucose into these cells plays monocarboxylic acid transport systems of these cells has been studied. The results of these studies will be correlated with in vivo work being conducted in this laboratory.
