Glial strategy for metabolic shuttling and neuronal function

Glial cells serve a variety of functions in nervous systems, some of which are activated by neurotransmitters released from neurons. Glial cells respo nd to these neurotransmitters via receptors, but also take up some of the t ransmitters to help terminate the synaptic process. Among these, glutamate uptake by glial cells is pivotal to avoid transmitter-mediated excitotoxici ty. Here, a new model is proposed in which glutamate uptake via the excitat ory amino acid transporter (EAAT) is functionally coupled to other glial tr ansporters, in particular the sodium-bicarbonate cotransporter (NBC) and th e monocarboxylate transporter (MCT), as well as other glial functions, such as calcium signalling, a high potassium conductance and CO2 consumption. T he central issue of this hypothesis is that the shuttling of sodium ions an d acid/base equivalents, which drive the metabolite transport across the gl ial membrane, cooperate with each other, and hence save energy. As a result , glutamate removal from synaptic domains and lactate secretion serving the energy supply to neurons would be facilitated and could operate with great er capacity. (C) 2000 John Wiley & Sons, Inc.