Lactate mimics only some effects of D-glucose on epileptic depolarization and long-term synaptic failure

Lactate supports normal synaptic function and may be neuroprotective following an anoxic insult. The present study investigated the effects of lactate on epileptic depolarization and long-term synaptic failure during a zero-magnesium-induced epileptic insult using the hippocampal slice preparation. In artificial cerebrospinal fluid (aCSF) containing 10 mM D-glucose, no epileptic depolarization was observed. At lower concentrations of D-glucose, epileptic depolarization occurred and often was followed by long-term synaptic failure. Low concentrations of lactate, in place of D-glucose, supported normal synaptic transmission. However, no concentration of lactate tested (up to 30 mM) blocked the occurrence of epileptic depolarization. High concentrations of lactate allowed for partial recovery of synaptic responses following epileptic depolarization. Reinstatement of D-glucose was necessary to observe this recovery. The results confirm that lactate can replace D-glucose in maintaining synaptic responses, but demonstrate that lactate cannot replace D-glucose in blocking an insult-induced depolarization. The inability of lactate to mimic all the effects of D-glucose is consistent with the notion of compartmentation of energy utilization within neurons.