Glutamate And GABA Flashcards
Is Glutamate an excitatory or inhibitor NT?
Excitatory
Where is glutamate most widely distributed in the body?
70% in the CNS
How is glutamate made in the neurone?
Glutamine is converted to glutamate by Glutaminase. Then it is degraded to alpha-oxoglutarate by transaminase
How it glutamate formed in Glia cells?
Alpha-oxoglutarate is converted to glutamate by GABA transaminase. It is degraded to Glutamine by Glutamine synthase
What are the three different types of vesicular-glutamate transporter pumps?
VGluT1
VGluT2
VGluT3
What is transported out of the vesicle in order for glutamate to be transported into the vesicle?
2 x H+ ions
How is the inside of the storage vesicle kept at a low pH?
Another proton pump/ATPase which pumps H+ into the cell against it’s concentration gradient. Needs ATP
Which channels opens after depolarisation occurs to release the glutamate form the vesicle?
Voltage gated Ca channels
What are the three ionotropic glutamate receptors? (Ion channels activated by glutamate)
NMDA cation channel - Na, K, Ca
AMPA cation channel - Na, K, (some Ca)
Kainate cation channel - N, K
What are the three metabotropic receptors what glutamate acts upon? (G-protein coupled receptors, Class C)
Group 1 - mGluR1 + mGluR5 couple to Gq and G11 G-proteins
Group 2 - mGluR2 + mGluR3 couple to Go and Gi G-proteins
Groups 3 - mGluR4 + mGluR6-8 couple to Go and Gi G-proteins
What is the structure of Inotropic glutamate receptor?
Heterotetromer
Bind to glutamate at the N terminus
3 alpha helices and inverted P loop
What is the structure of the G-coupled glutamate receptors?
7 transmembrane domains
Binding site outside on the N terminus
Coupling region on the third intracellular loop
Activate second messenger system
How is glutamate recycled?
Either taken up into the glial cells where it is converted to glutamine or repackaged into vesicles in the neurone
How is glutamate removed from the synaptic cleft?
EAAT
Which drugs work on the NMDA glutamate receptor?
Ketamine - channel blocker
Meantime - competitive antagonist
Which drug works on the AMPA glutamate receptor?
Perampanel - noncompetitive antagonist
Which recreational drugs involved the glutamate receptors?
Ketamine
PCP (phencyclidine)
Which diseases can be therapeutically controlled by manipulation of the glutamate receptors?
Epilepsy
Alzheimer’s
Anaesthetic
Is GABA an inhibitory or excitatory neurotransmitter?
Inhibitory
How is GABA made?
From glutamate via the glutamic acid decarboxylase enzyme (GAD)
What is the name of the transporter which concentrates GABA into it’s storage vesicle?
Vesicular GABA transporter
What is needed for release of GABA from the vesicles?
Ca influx
Which ionotropic receptors are activated by GABA?
GABAa receptor - anion Cl-
Which metabotropic receptors do GABA work on?
GABAb receptors coupled to Gi and Go proteins
What is the structure of the ionotropic receptor GABAa?
Heteropentomer - 5 subunits
2 binding sites for GABA
Cl- pore in the middle so when GABA binds, Cl- ions can flow through in the cell
What is the structure of the metabotropic GABAb receptor?
7 transmembrane units
GABA binds to N terminus
Third loop modifies cell’s biochemistry
How is GABA removed from the synaptic cleft?
Via the reuptake protein
Which reuptake proteins are present on neurones?
GAT1
Which reuptake proteins are on astrocytes, in particular glial cells?
GAT3
How is GABA degraded?
It is broken down to Succinic semialdehyde via the GABA transaminase
Which drugs act via the GABAa receptor?
Benzodiazepines, alcohol and some general anaesthetics (propofol) are all positive allosteric modulators
Which drugs work via the GABAb receptors?
Baclofen (agonist)
Saclofen (competitive antagonist)
Which two drugs used in Epilepsy work via the GABA system and how?
Tiagabine - blocks GAT
Vigabatrine - blocks GABA-t
Which recreational drugs work via the GABA system?
Barbiturates
Nitrous oxide
