GLUTAMATE TRANSPORT AND STORAGE IN SYNAPTIC VESICLES

Glutamate plays an important metabolic role in virtually every vertebr ate cell. In particular, glutamate is the most common excitatory neuro transmitter in the vertebrate central nervous system. As such, the mec hanism by which glutamate is diverted from its normal metabolic activi ties toward its role as a neurotransmitter has, in recent years, been systematically investigated. In glutamatergic nerve endings, synaptic vesicles accumulate and store a proportion of the cellular glutamate p ool and, in response to appropriate signals, release glutamate into th e synaptic cleft by exocytosis. Glutamate accumulation is accomplished by virtue of a glutamate uptake system present in the synaptic vesicl e membrane. The uptake system consists of a transport protein, remarka bly specific for glutamate, and a vacuolar-type H+-ATPase, which provi des the coupling between ATP hydrolysis and glutamate transport. The p recise manner in which the glutamate transporter and H+-ATPase operate is currently the subject of debate. Recent data relevant to this deba te are reviewed in this article. Additionally, pharmacological agents thought to specifically interact with the vesicular glutamate transpor ter are discussed. Finally, a newly discovered, endogenous inhibitor o f vesicular uptake, inhibitory protein factor (IPF), is discussed with some speculations as to its potential role as a presynaptic modulator of neurotransmission.