Glutamate
Glutamate, an amino acid, is the most common excitatory neurotransmitter in the nervous system.
- role in central nervous system
- role in peripheral nervous system
- receptors and signaling
- agonists and antagonists
- role in disease
Role in Central Nervous System
- glutamate and aspartate primarily activate fast, ionotropic cation channels, generating small EPSPs. Many such EPSPs need to sum together to trigger an action potential. The threshold number varies but is roughly in the range of 10-100.
- Glutamate signaling is thought to underly learning and memory
- glutamate overexcitation is also thought to be involved in cell damage and death in Huntington's disease and following acute brain injury, as follows stroke or excessive seizures
Role in the Peripheral Nervous System
Receptors and Signaling
Glutamine is converted to glutamate by glutaminase in the presynaptic cell, stored, and released.
Glutamate can act on four major classes of receptors.
AMPA receptors are ionotropic and are found in most excitatory synapses in the brain. They let Na+, K+, and very little Ca2+.
NMDA receptors, of which there are many, are also ionotropic. During hyperpolarization, NMDA receptors are blocked by magnesium, only opening above - 60 mV. This makes NMDA channels both ligand gated and voltage gated. They co-exist with AMPA-gated channels, opening more slowly once other channels have opened.
kainate receptor channels are a mystery.
mGlu Receptors are metabotropic.
Surrounding glial cells take up glutamate from the synapse, convert in back to glutamine, and return it to pre-synaptic cells.
Agonists and Antagonists
Agonists
Antagonists
Role in Disease