The conventional view that glucose is the substrate for neuronal
energy metabolism has been recently challenged by the “lactate
shuttle” hypothesis in which glutamate cycling in glial cells
drives all neuronal glucose metabolism. According to this view,
glutamate released by activated retinal neurons is transported into
Müller (glial) cells where it triggers glycolysis. The lactate
released by Müller cells serves as the energy substrate for
neuronal metabolism. Because the L-Glutamate/aspartate transporter
(GLAST) is the predominant, Na+-dependent, glutamate
transporter expressed by Müller cells, we have used GLAST-knockout
(GLAST−/−) mice to examine the
relationship between lactate release and GLAST activity in the retina.
We found that glucose uptake and lactate production by the
GLAST−/− mouse retina was similar
to that observed in the wild type mouse retina. Furthermore, addition
of 1 mM glutamate and NH4Cl to the incubation medium did not
further stimulate glucose uptake in either case. When lactate release
was measured in the presence of the lactate uptake inhibitor,
α-cyano-4-hydroxycinnamate, there was no significant change in the
amount of lactate released by retinas from
GLAST−/− mice compared to the wild
type. Finally, lactate release was similar under both dark and light
conditions. These results show that lactate production and release is
not altered in retinas of GLAST−/−
mice, which suggests that metabolic coupling between photoreceptors and
Müller cells is not mediated by the glial glutamate transporter,
GLAST.
Basigin gene products form a novel cell adhesion system between Muller cells and photoreceptors in the mouse retina
