Glutamate

L-Glutamate is the main excitatory neurotransmitter in the CNS.   It is found throughout the CNS.

Metabolism and Release

Glutamate in the CNS comes mainly from glucose via the Kreb’s cycle or from glutamine syntesised by glial cells.  The metabolism of glutamate is directly linked to that of GABA (the primary inhibitory neurotransmitter).  This makes targeting drugs difficult as to affect one will undoubtedly affect the other.

Green arrows represents pathways in GABAergic neurons and orange arrows represent pathways in glutaminergic neurons. see http://www.pnas.org/content/102/15/5588/F1.expansion.html

Glutamate is stored in synaptic vesicles and released by Ca(2+)-dependent exocytosis.  Released glutamate is taken up by Na+/H+/K+ dependent transporters.  From there it is stored in synaptic vesicles once more.  Its action is terminated either by reuptake into adjacent glial cells (main route), which can convert it to inactive glutamine, or reuptake into the transmitting neuron to be recycled.

Extracellular concentrations of glutamate are kept low by transporter proteins in the plasma membrane (ATP-mediated) and then cytosolic concentrations are also kept low by storing glutamate in vesicles via ATP mediated vesicular transporters.

Glutamate is the main excitatory neurotransmitter in the brain and is crucial for normal synaptic communication.  However, too much glutamate is known to be damaging and sometimes lethal to cells- a process known as excitotoxicity.

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