OCB03-2008 GABA Flashcards
What does GABA stand for?
γ-amino butyric acid
What is the role of GABA in the central nervous system?
Major inhibitory neurotransmitter (~50% of pathways) in CNS
What two defects is GABA implicated in?
Epilepsy (loss of inhibition)
Huntington’s disease - neurodegeneration of GABAergic spiny neurons
How is GABA formed?
From glutamate by glutamic acid decarboxylase (GAD) found only in GABA synthesising neurons
Briefly describe release and reuptake processes of GABA.
(Similar to glutamate)
Stored in vesicles and exocytosed due to calcium influx
Diffuses then is taken up into astrocytes and neurons which terminates action
What is the function of GABA transaminase?
GABA –> succinic semi aldehyde
What enzyme catalyses the reaction of GABA –> succinic semi aldehyde?
GABA transaminase
What is the function of glutamic acid decarboxylase?
Glutamate –> GABA
What are the two types of GABA receptor?
Ionotropic = GABA A receptors
Metabotropic = GABA B receptors
Where are GABA A receptors found?
Postsynaptic neurons
What type of receptor does benzodiazepine act on?
GABA A receptors
Where are GABA B receptors found?
Pre and postsynaptically
Describe a GABA A receptor. (5)
Ionotropic
Postsynaptic
Mediates fast inhibition
5 subunits
Selective for anions
What are the five subunits of a GABA A receptor?
2 x α
2 x β
1 x γ
What happens when GABA binds to a GABA A receptor?
Conformational change = pore opens
Anions/Cl- enters cell down concentration gradient
Hyperpolarisation or clamping of voltage near resting potential
What can blockages of GABA A receptors result in?
Hyperactivity of neurons = convulsions
What drugs (4) can enhance the opening of GABA A receptors and what is their general mode of action?
Ethanol
Benzodiazepine
Barbituates
General anaesthetics
Allosteric mode of action
What allosteric site do benzodiazepines bind to on GABA A receptors?
Where α and γ subunits interact
What effect do benzodiazepines have on GABA A receptors?
Increase probability of channel opening with no effect on channel properties
What type of drug is midazolam and what does it do/used for?
Benzodiazepine
Short-acting, used for sedation or anti-anxiety drug during minor invasive procedures
What do fluorine volatile general anaesthetics do?
Promote GABA A channel activation/opening
What type of drug is enflurane?
Fluorine volatile general anaesthetic
Describe a GABA B receptor. (3)
Metabotropic/7TMGPCR
Coupled to Gi
Pre and postsynaptic
What are the general functions of a GABA B receptor?
α-GTP inhibits adenylyl cyclase
βγ subunit coupled to ion channels
What happens when a presynaptic GABA B receptor is activated?
βγ subunit inhibits voltage-gated Ca channels to decrease NT release
What happens when a postsynaptic GABA B receptor is activated?
βγ subunit increases opening of K channels = IPSP
Reduced firing of AP
What is baclofen?
GABA B agonist used to treat muscle spasticity
What is the general effect of activating a GABA B receptor?
Long-lasting inhibition
