FIGURE 2.

Hypothesized mechanism for glutamate transport-dependent vasodilation. After neuronal depolarization, most of the glutamate released into the extracellular space is cleared by the astrocytic glutamate transporters, GLT-1 and GLAST. Several groups have shown that the simultaneous influx of Na⁺ that drives glutamate uptake can trigger reversed operation of the Na⁺/Ca²⁺ exchangers and increase in cytosolic Ca²⁺. This Ca²⁺ can activate nitric oxide synthetase (NOS), phospholipase 2 (which generates arachidonic acid and can activate cyclooxygenase, Cox1 and Cox2), or other Ca²⁺-activated processes. These pathways have been linked to vasodilation in several studies (for references, see results). The pharmacologic agents used to test each of these targets is also included.