Vesicular glutamate transporters are H-anion exchangers that operate at variable stoichiometry.

Vesicular glutamate transporters accumulate glutamate in synaptic vesicles, where they also function as a major Cl efflux pathway. Here we combine heterologous expression and cellular electrophysiology with mathematical modeling to understand the mechanisms underlying this dual function of rat VGLUT1. When glutamate is the main cytoplasmic anion, VGLUT1 functions as H-glutamate exchanger, with a transport rate of around 600 s at -160 mV.