Glutamate released from intracellular vesicles into the synaptic cleft binds and activates NMDA receptors (NMDA R) on postsynaptic neurons. Activation of NMDA R plays an important role in synaptic plasticity, memory, and other neurological functions. However, NMDA R can be over-activated by excess glutamate in the synaptic cleft. Over activation of NMDA R induces excitotoxicity, a term used to describe cell death induced by excess excitory amino acids such as glutamate. To prevent excitotoxicity, glutamate transporters of the excitory amino acid transporter (EAATs) class, rapidly remove glutamate from the synaptic cleft. However, since intracellular glutamate concentrations are much higher than extracellular concentrations, EAATs require energy to move glutamate against its concentration gradient. This energy is provided by coupling the inward transport of glutamate to the transport of ions along their concentration gradient. Specifically, the inward transport of one glutamate is coupled to the co-transport of three sodium ions and one proton and the counter-transport of one potassium ion. Tocris provides an extensive array of small molecule agonists and antagonists to support glutamate transporter research including a ligand set which contains five different inhibitors of EAATs (Catalog # 1830).
Vesicular glutamate transporters (VGLUTs) and cystine/glutamate transporters (xCT) represent two additional classes of glutamate transporters. VGLUTs are responsible for packaging of glutamate into intracellular vesicles. In contrast, xCTs transport one glutamate out of the cell while transporting one cystine into the cell. Although the physiological role of xCT transporters remains controversial, they are assumed to function as an uptake mechanism for glutathione synthesis.