E12 Neuronal energy metabolism

Topic

The electrical functioning of the neuron—including the generation and propagation of action potentials, ion pumping, and synaptic transmission—entails an energy cost that the neuron meets through cellular energy production via two pathways: glycolysis and mitochondrial oxidative phosphorylation. Both pathways follow Michaelis-Menten kinetics based on the neuron's availability of glucose and oxygen: energy production via either pathway increases with glucose or oxygen availability when levels are low, but plateaus and ceases to grow proportionally once availability is sufficiently high.

In addition to glucose, the neuron utilizes a complementary energy substrate: lactate. This is supplied via the astrocyte-neuron lactate shuttle, a net flow of lactate produced by the astrocyte and delivered to the neuron.

The neuron's demand for cellular energy scales with its electrical activity, as maintaining the ionic gradients dissipated during each action potential is the primary consumer of the neuron's cellular energy: the more electrical activity the neuron generates, the more ionic gradients it dissipates, and the greater the cellular energy demand it must meet.

The balance between the neuron's cellular energy production and demand determines whether it maintains a stable energy state—quantified by Atkinson's energy charge index: the closer the energy demand comes to exceeding production, the further the neuron drifts from that stable energy state. This balance between cellular energy production and demand is crucial for understanding conditions of metabolic stress, such as those occurring during ischemic stroke. Ultimately, it is this very neuron—with its energy costs met by glycolysis, oxidative phosphorylation, and lactate supplied by the astrocyte—that must maintain the balance between cellular energy production and demand in order to preserve its stable energy state.

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