Strategies for metabolic exchange between glial cells and neurons

The brain is a major energy consumer and dependent on carbohydrate and oxygen supply. Electrical and synaptic activity of neurons can only be sustained given sufficient availability of ATP. Glial cells, which have long been assigned trophic functions, seem to play a pivotal role in meeting the energy requirements of active neurons. Under conditions of high neuronal activity, a number of glial functions, such as the maintenance of ion homeostasis, neurotransmitter clearance from synaptic domains, the supply of energetic compounds and calcium signalling, are challenged. In the vertebrate brain, astrocytes may increase glucose utilization and release lactate, which is taken up and consumed by neurons to generate ATP by oxidative metabolism. The CO₂ produced is processed primarily in astrocytes, which display the major activity of carboanhydrase in the brain. Protons and bicarbonate in turn may contribute to drive acid/base-coupled transporters. In the present article a scenario is discussed which couples the transfer of energy and the conversion of CO₂ with the high-affinity glutamate uptake and other transport processes at glial and neuronal cell membranes. The transporters can be linked to glial signalling and may cooperate with each other at the cellular level. This could save energy, and would render energy exchange processes between glial cells and neurons more effective. Functions implications and physiological responses, in particular in chemosensitive brain areas, are discussed.