Flashcards in Principles of GABA-ergic Transmission Deck (36)
What are the two main inhibitory amino acid neurotransmitters?
What are the main excitatory amino acid neurotransmitters?
(L-homocysteine – sulphur containing)
What type of amino acids are the inhibitory neurotransmitters?
What type of amino acids are the excitatory neurotransmitters?
Why is GABA called GABA?
Gamma amino butyric acid
This is because the amino group is on the gamma carbon of GABA
Describe the distribution of GABA neurones.
Dorsal horn of spinal cord
Relatively little in the PNS
Describe the morphology of GABA neurones.
They are generally short inhibitory interneurons
Where do you find longer GABA tracts?
What is the main action of GABA neurones?
Widespread inhibitory action in the CNS
What are the main functions of GABA neurones in terms of CNS activity?
What is the precursor for GABA and what enzyme converts it to GABA?
Glutamic acid decarboxylase (GAD)
Where is this enzyme found?
This enzyme is exclusive to GABA nerve terminals – it is a marker for GABA neurones
What product of the Krebs’ cycle gives rise to glutamate?
How is GABA broken down?
Initially by GABA-T (GABA transaminase) to succinic semialdehyde
Succinic semialdehyde is broken down by succinic semialdehyde dehydrogenase (SSDH) to succinate
Succinate then enters the Krebs’ cycle
Describe the release of GABA from GABAergic nerve terminals.
What are the two main GABA receptors and why type of receptorsare they?
GABA-A = type 1 – ionotropic
GABA-B = type 2 – metabotropic
How is GABA inactivated?
What are the uptake mechanisms dependent on?
Where are the transport proteins for GABA found?
What type of enzymes are the enzymes that break down GABA?
What type of enzyme is GAD?
Name two drugs that are used as anti-convulsants that decrease the metabolism of GABA.
Sodium valproate (acts on GABA-T and SSDH (but more so on SSDH))
Vigabatrin (selective GABA-T inhibitor)
Where are GABA-A receptors found?
Describe the structure of GABA-A receptors.
They are ionotropic receptors (type 1)
They have a pentameric structure consisting of the following subunits:
2 x alpha
2 x beta
1 x gamma
What is the mechanism of action of GABA-A receptors?
GABA binding causes opening of the chloride channel leading to chloride influx
This causes hyperpolarisation of the postsynaptic neurone (inhibitory post-synaptic potential)
This causes inhibition of firing
Name two agonists of GABA-A.
Name two antagonist of GABA-A
Bicuculline (competitive antagonist)
Picrotoxin (non-competitive antagonist)
What effect do the antagonists have?
They are convulsants
They are used experimentally but not therapeutically
Where are GABA-B receptors located?