Glycolysis regulates the induction of lactate utilization for synaptic potentials after hypoxia in the granule cell of guinea pig hippocampus

• Published in: Neuroscience research 2004-12, Vol.50 (4), p.467-474
• Main Authors: Takata, Toshihiro, Yang, Bo, Sakurai, Takashi, Okada, Yasuhiro, Yokono, Koichi
• Format: Article
• Language: English
• Subjects: Action Potentials - physiology; Adenosine triphosphate; Adenosine Triphosphate - biosynthesis; Animals; Calcium - metabolism; Calcium - pharmacology; Calcium Channel Blockers - pharmacology; Cell Hypoxia - physiology; Dentate Gyrus - metabolism; Energy Metabolism - physiology; Excitatory Amino Acid Antagonists - pharmacology; Field potential; Glucose - metabolism; Glutamate release; Glycolysis; Glycolysis - physiology; Guinea Pigs; Hippocampus - metabolism; Hypoglycemia - metabolism; Hypothermia, Induced; Lactate; Lactic Acid - metabolism; Neurons - metabolism; NMDA receptor; Organ Culture Techniques; Presynaptic Terminals - metabolism; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors; Receptors, N-Methyl-D-Aspartate - metabolism; Synaptic Transmission - physiology; Voltage-sensitive calcium channel
• ISSN: 0168-0102; 1872-8111
• DOI: 10.1016/j.neures.2004.08.008

Lactate is considered an alternative substrate that is capable of replacing glucose in maintaining synaptic function in adult neurons. But, we found recently that lactate could be utilized for maintenance of synaptic potentials only after the activation of NMDA and voltage-dependent-calcium channel during glucose deprivation. To clarify more on the relationship between glycolysis and induction of lactate utilization, we tested lower concentration of glucose with hypoxia to induce a relative shortage of anaerobic energy production. Population spikes are not maintained with lactate following hypoxia in 10 mM glucose medium, but are maintained at their original levels with lactate after exposure to hypoxia in lower concentration (5 mM) of glucose. Hypothermia during low glucose-hypoxia, bath application of the NMDA channel blocker and the voltage-sensitive calcium channel blocker, as well as the omission of extracellular calcium prevented the induction of the lactate-supported population spikes. ATP levels in the tissue slices are relatively preserved in the conditions that block the induction of lactate-supported population spikes. From these observations, we propose that the energy source for maintenance of synaptic function in adult neuron changes from adult form (glucose alone) to immature one (glucose and/or lactate) after short of glucose supply.