Glutamate and GABA

Glutamate

The major excitatory neurotransmitter in the CNS that is synthesized from glutamine.

Glutaminase

The enzyme responsible for converting glutamine into glutamate.

Glutamate transpoters (VGLUT1, VGLUT2, VGLUT3)

The specific transporter in the vesicle membrane only found on glutaminergic neurons that recognize and move glutamate into synaptic vesicles.

Gliotransmission

The process by which astrocytes release glutamate they have taken up from the extracellular space, express glutamate receptors, and respond to activation of those receptors.

Excitatory amino acid transporters (EAAT1 - EAAT5)

The glutamate transporters on neurons and atsrocytes that rapidly remove both glutamate and aspartate after their release.

Glutamine synthetase

The enzyme that breaks down glutamate into glutamine after removal of glutamate by astrocytes. Glutamine is produced to inactivate glutamate but is then transported back to the neuron for glutamate synthesis.

Pyramidal cells

The large excitatory neurons that use glutamate and are the major output neurons of the cortex.

AMPA and Kainate receptors

The ionotropic glutamate receptors that allow the flow of Na⁺, depolarizing the cell.

NMDA receptors

The ionotropic glutamate receptors that allow the flow of both Na⁺ and Ca²⁺. To open the channel, both glutamate and glycine must bind at the same time. There are additional non-competitive binding sites within the channel

mGluR1

The metabotropic glutamate receptors that activate the phosphoinositide second-messenger system.

mGluR2 & mGluR3

The metabotropic glutamate receptors that inhibit cAMP formation. Many are presynaptic autoreceptors or heteroreceptors.

Phencyclidine (PCP) and Ketamine

The hallucinogenic drugs that act as non-competitive antagonists within the NMDA receptor channel.

Menmantine (Namenda)

The drug that acts as a non-competitve antagonist within the NMDA receptor channel that is used to treat Alzheimer’s disease.

GABA

The major inhibitory amino acid transmitters that is synthesized from glutamate.

Glutamic acid decarboxylase (GAD)

The enzyme responsible for converting glutamate into GABA.

Vesicular GABA transporters

The membrane protein responsible for loading GABA and glycine into synaptic vesicles in inhibitory neurons.

GAT-1, GAT-2,GAT-3

The specialized protein transporter that removes GABA from the synaptic cleft.

GABA aminotransferase (GABA-T)

The enzyme in GABAergic neurons and astrocytes that is responsible for metabolizing GABA into glutamate.

Tiagabine (Gabitril)

The drug that elevates extracellular GABA levels by acting as a selective GAT-1 inhibitor and is used for treating epilepsy.

Vigabatrin (Sabril)

The drug that elevates extracellular GABA levels by acting as an irreversible GABA-T inhibitor.

GABA Neurons

The local interneurons with the cerebral cortex, hippocampus, and substantia nigra. Also can be found in projection neurons in the striatum.

Ionotropic GABA_A Receptors

The ionotropic channels that allow Cl^- into the cell, causing hyperpolarization and inhibition of the postsynaptic cell. Consists of five subunits in various combinations of four types - α, β, γ, δ.

Metabotropic GABA_B Receptors

The metabotropic channels that inhibit cAMP formation and open K⁺ channels. They can have effects on behavioral functions such as learning and memory, anxiety and depression, etc.

Muscimol

The drug found in mushrooms that act as a GABA_A agonist and has hallucinogenic effects.

Benzodiazepines (BDZ)

The drug that has potentiating effects on the GABA_A receptor and increases the potency of GABA to open the receptor channel

Anesthetics

The class of drugs that allosterically modulate GABA_A receptor channel opening and at high concentrations can open the channel even in the absence of GABA.