Neuronal glucose but not lactate utilization is positively correlated with NMDA-induced neurotransmission and fluctuations in cytosolic Ca2+ levels.
Although the brain utilizes glucose for energy production, individual brain cells may to some extent utilize substrates derived from glucose. Thus, it has been suggested that neurons consume extracellular lactate during synaptic activity. However, the precise role of lactate for fueling neuronal activity is still poorly understood. Recently, we demonstrated that glucose metabolism is up-regulated in cultured glutamatergic neurons during neurotransmission whereas that of lactate is not. Here, we show that utilization of glucose but not lactate correlates with NMDA-induced neurotransmitter glutamate release in cultured cerebellar neurons from mice. Pulses of NMDA at 30, 100, and 300 microM, leading to a progressive increase in both cytosolic [Ca2+] and release of glutamate, increased uptake and metabolism of glucose but not that of lactate as evidenced by mass spectrometric measurement of 13C incorporation into intracellular glutamate. In this manuscript, a cascade of events for the preferential neuronal utilization of glucose during neurotransmission is suggested and discussed in relation to our current understanding of neuronal energy metabolism.
Bak
Lasse K
LK
Department of Pharmacology and Pharmacotherapy, Faculty of Pharmaceutical Sciences, University of Copenhagen, Copenhagen, Denmark. laba@farma.ku.dk
Walls
Anne B
AB
Schousboe
Arne
A
Ring
Avi
A
Sonnewald
Ursula
U
Waagepetersen
Helle S
HS
D000818:Animals; D000963:Antimetabolites / Q000378:metabolism; D001224:Aspartic Acid / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism*; D003847:Deoxyglucose / Q000378:metabolism; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D019344:Lactic Acid / Q000378:metabolism*; D008293:Malates / Q000378:metabolism; D051379:Mice; D016202:N-Methylaspartate / Q000494:pharmacology*; D009474:Neurons / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects*
D000963:Antimetabolites; D018690:Excitatory Amino Acid Agonists; D008293:Malates; D018377:Neurotransmitter Agents; D001224:Aspartic Acid; D019344:Lactic Acid; D016202:N-Methylaspartate; C030298:malic acid; D003847:Deoxyglucose; D005947:Glucose; D002118:Calcium