Molecular and cellular physiology of sodium-dependent glutamate transporters.

Glutamate is the major excitatory transmitter in the vertebrate brain. After its release from presynaptic nerve terminals, it is rapidly taken up by high-affinity sodium-dependent plasma membrane transporters. While both neurons and glial cells express these excitatory amino acid transporters (EAATs), the majority of glutamate uptake is accomplished by astrocytes, which convert synaptically-released glutamate to glutamine or feed it into their own metabolism. Glutamate uptake by astrocytes not only shapes synaptic transmission by regulating the availability of glutamate to postsynaptic neuronal receptors, but also protects neurons from hyper-excitability and subsequent excitotoxic damage. In the present review, we provide an overview of the molecular and cellular characteristics of sodium-dependent glutamate transporters and their associated anion permeation pathways, with a focus on astrocytic glutamate transport. We summarize their functional properties and roles within tripartite synapses under physiological and pathophysiological conditions, exemplifying the intricate interactions and interrelationships between neurons and glial cells in the brain.