Energy sources for glutamate neurotransmission in the retina: absence of the aspartate/glutamate carrier produces reliance on glycolysis in glia.
The mitochondrial transporter, the aspartate/glutamate carrier (AGC), is a necessary component of the malate/aspartate cycle, which promotes the transfer into mitochondria of reducing equivalents generated in the cytosol during glycolysis. Without transfer of cytosolic reducing equivalents into mitochondria, neither glucose nor lactate can be completely oxidized. In the present study, immunohistochemistry was used to demonstrate the absence of AGC from retinal glia (Müller cells), but its presence in neurons and photoreceptor cells. To determine the influence of the absence of AGC on sources of ATP for glutamate neurotransmission, neurotransmission was estimated in both light- and dark-adapted retinas by measuring flux through the glutamate/glutamine cycle and the effect of light on ATP-generating reactions. Neurotransmission was 80% faster in the dark as expected, because photoreceptors become depolarized in the dark and this depolarization induces release of excitatory glutamate neurotransmitter. Oxidation of [U-14C]glucose, [1-14C]lactate, and [1-14C]pyruvate in light- and dark-adapted excised retinas was estimated by collecting 14CO2. Neither glucose nor lactate oxidation that require participation of the malate/aspartate shuttle increased in the dark, but pyruvate oxidation that does not require the malate/aspartate shuttle increased to 36% in the dark. Aerobic glycolysis was estimated by measuring the rate of lactate appearance. Glycolysis was 37% faster in the dark. It appears that in the retina, ATP consumed during glutamatergic neurotransmission is replenished by ATP generated glycolytically within the retinal Müller cells and that oxidation of glucose within the Müller cells does not occur or occurs only slowly.
Xu
Y
Y
Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA.
Ola
M S
MS
Berkich
D A
DA
Gardner
T W
TW
Barber
A J
AJ
Palmieri
F
F
Hutson
S M
SM
LaNoue
K F
KF
D000255:Adenosine Triphosphate / Q000096:biosynthesis; D026922:Amino Acid Transport Systems, Acidic / Q000378:metabolism; D000818:Animals; D017920:Antiporters / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism; D006019:Glycolysis / Q000502:physiology*; D008293:Malates / Q000378:metabolism; D008297:Male; D053858:Metabolic Networks and Pathways / Q000502:physiology; D009457:Neuroglia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D009924:Organ Culture Techniques; D010786:Photoreceptor Cells / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000166:cytology / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*; D014785:Vision, Ocular / Q000502:physiology / Q000528:radiation effects
D026922:Amino Acid Transport Systems, Acidic; D017920:Antiporters; D008293:Malates; C051046:aspartate-glutamate carrier; D005973:Glutamine; D018698:Glutamic Acid; C030298:malic acid; D000255:Adenosine Triphosphate; D005947:Glucose