1 research outputs found
Novel model of neuronal bioenergetics: postsynaptic utilization of glucose but not lactate correlates positively with Ca2+ signalling in cultured mouse glutamatergic neurons
We have previously investigated the relative roles of extracellular glucose
and lactate as fuels for glutamatergic neurons during synaptic activity. The
conclusion from these studies was that cultured glutamatergic neurons utilize
glucose rather than lactate during NMDA (N-methyl-d-aspartate)-induced
synaptic activity and that lactate alone is not able to support neurotransmitter
glutamate homoeostasis. Subsequently, a model was proposed to explain these
results at the cellular level. In brief, the intermittent rises in intracellular
Ca2+ during activation cause influx of Ca2+ into the
mitochondrial matrix thus activating the tricarboxylic acid cycle dehydrogenases.
This will lead to a lower activity of the MASH (malate–aspartate shuttle),
which in turn will result in anaerobic glycolysis and lactate production rather
than lactate utilization. In the present work, we have investigated the effect
of an ionomycin-induced increase in intracellular Ca2+ (i.e. independent
of synaptic activity) on neuronal energy metabolism employing 13C-labelled
glucose and lactate and subsequent mass spectrometric analysis of labelling
in glutamate, alanine and lactate. The results demonstrate that glucose utilization
is positively correlated with intracellular Ca2+ whereas lactate
utilization is not. This result lends further support for a significant role
of glucose in neuronal bioenergetics and that Ca2+ signalling may
control the switch between glucose and lactate utilization during synaptic
activity. Based on the results, we propose a compartmentalized CiMASH (Ca2+-induced
limitation of the MASH) model that includes intracellular compartmentation
of glucose and lactate metabolism. We define pre- and post-synaptic compartments
metabolizing glucose and glucose plus lactate respectively in which the latter
displays a positive correlation between oxidative metabolism of glucose and
Ca2+ signalling