GABA Flashcards
GABA is the principle … transmitter in the CNS
Inhibitory
GABA synthesis
Produced via enzymatic synthesis from glucose via Kreb’s cycle.
In nerve terminal
GABA storage
Taken up by vesicular GABA transporters and stored until calcium dependent exocytosis occurs
Reuptake of GABA
Reuptake by GABA Transporters (GAT)
The rest is converted into succinic semialdehyde by GABA transaminase
Or can be taken up by vesicles in glial cells and converted there.
Location of GABA neurons
Cerebellum, basal ganglia, hippocampus, hypothalamus, cortex.
Types of neurons GABA found in
Prominent roles in local interneurons.
Also found in relay and projection neurons
Local interneurons
Have short projections and regulate the interactions of the local circuit.
Connections are limited to other neurons in the local area.
GABA A
- Ligand gated ion channels
- Permeable to Cl- ions
- Hyperpolarises membrane
- Primarily postsynaptic
- Mediate fast inhibition
GABA B
- G-protein-coupled receptors (GPCR)
- Coupled to Ca2+ and K+ ion channels
- Pre and postsynaptic
- Mediate slow inhibition (seconds-minutes)
- Also inhibit transmitter release
GABA A action
GABA opens channel
Low intracellular Cl- causes an inward current of Cl
This causes an inhibitory postsynaptic potential (IPSP), which makes the neuron less likely to fire
GABA A structure
Pentameric combinations of subunits arranged to make a channel
Main receptor in our brain has two α, two β and one γ-subunit
GABA binds between α and β, so two molecules are needed for activation
Subunits in GABA A
Each subunit has 4 trans-membrane segments
TM2 is the pore forming segment which faces into the channel and contributes to the ion selectivity
Pharmacology of GABA A
Benzodiazepine binds and potentiates GABA increasing frequency of channel opening
Barbiturates/anaesthetics bind and potentiate GABA, prolonging channel opening
Channel blocking sites block Cl- permeability
GABA B receptors are _ coupled
Gαi/o
GABA B are GCPRs with _ transmembrane segments
7
GABA B receptors couple to and open _ channels in _ synaptic neurons
K+, post
Allows K+ to leave cell
Hyperpolarisation
Gβγ subunit closes _-channels in _synaptic terminals
Ca2+, pre
Formation of GABA B
R1 in the endoplasmic reticulum binds GABA, inducing change in proteins, inducing change in cytoplasm.
Dimerises with R2 (where G protein couples) in the cell membrane to form functional GABA_B R
GABA B receptors are obligatory _
Heterodimers
Presynaptic GABA _ can mediate the effect of post synaptic GABA _
B, A
GABA B agonists are used to treat …
spasticity by activating postsynaptic GABABR on motor neurones
GABA B antagonists are used to treat
epilepsy by blocking postsynaptic GABA B R on GABA neurones to prevent the reduction of GABA release and to increase synaptic inhibition.
