Glutamate transporters are responsible for clearing the transmitter from the synaptic cleft after exocytotic release. But transporters also carry ions, and it has been shown that their activation can generate ionic currents in the postsynaptic membrane and in glial cells. Some glutamate transporters are also present in the presynaptic terminal, raising the possibility that they affect the presynaptic membrane potential, and thereby modify release probability through such an ionic current. Unfortunately, recording transporter-mediated currents from presynaptic terminals is a difficult task, owing to their small size. In a recent paper published in The Journal of Neuroscience, Palmer et al. get around this limitation by recording from two types of large presynaptic terminals, showing that glutamate transporters can indeed elicit presynaptic currents.

The authors recorded from the large terminals of the bipolar cells of the goldfish retina, and found that a presynaptic anionic current accompanied glutamate release from this synapse. This current had a large unitary conductance and was sensitive to glutamate transporter inhibitors with a pharmacological profile that pointed to the excitatory amino acid transporter 5 (EAAT5) as the molecular culprit. Importantly, this current was conspicuously absent from the second type of terminal from which Palmer et al. recorded — the calyx of Held — indicating that there is a degree of specificity to the putative function of presynaptic glutamate transporters and their associated current.

On the basis of the properties of this anionic conductance, the authors calculated that the activation of about 50 transporters after the fusion of about 600 synaptic vesicles would hyperpolarize the presynaptic membrane by about 7 mV, an amount that might affect the release properties of the synapse. Although future studies should probe the validity of this calculation, the data of Palmer et al. highlight the importance of a little-recognized mechanism to regulate presynaptic function.