22- GABA Flashcards
what is GABA?
the major inhibitory neurotransmitter in the CNS
describe the synthesis of GABA
synthesised in nerve terminals with glutamate as its precursor
glutamate, catalysed by GAD/ glutamate decarboxylase with pyridoxal phosphate as a co-factor, is decarboxylated into GABA
what is pyridoxal phosphate derived from?
vitamin B6
describe how GABA is stored
GABA is synthesised in nerve terminals and transported by VIAATs into synaptic vesicles for storage
vesicles have an oval appearance
VIAAT = vesicular inhibitory amino acid transporters
describe GABA re-uptake - transporter(s) involved?
GABA re-uptake occur from the synapse into the pre-synaptic neurone allowing it to be recycled
re-uptake by GAT transporter which sit on the pre-synaptic terminal
neurones and glial cells have different isoforms of high-affinity Na+ dependent GABA reuptake GAT
neurones predominantly have GAT-1, glial cells have GAT-3. other isoforms are also present.
describe the degradation of GABA
two step process involving two enzymes to terminate GABA activity
GABA broken down into succinic semialdehyde, catalysed by GABA transaminase
succinic semialdehyde broken down into succinic acid, catalysed by SSADH
in what three ways can GABA activity be terminated at the synapse?
GABA can diffuse away from the synapse, re-uptake OR degradation
what two enzymes are involved in GABA degradation?
GABA-T = GABA transaminase
SSADH = succinic semialdehyde dehydrogenase
what is the name of the transporter responsible for GABA reuptake? how does it differ in neurones and glial cells?
GAT
different isoforms predominantly in neurones and glial cells. neurones = GAT-1; glial cells = GAT-3
what enzyme and co-factor is involved in GABA synthesis?
enzyme = glutamate decarboxylase
co-factor = pyridoxal phosphate
what are the two types of GABA receptor?
GABA-A ionotropic receptor (LG ion channel)
GABA-B metabotropic receptor (GCPR)
how do GABA-A and B receptors work in inhibiting action potential firing?
GABA-A = GABA binds to receptor, ion channel core opens allowing Cl- influx
GABA-B = GABA binds to GCPR receptor, activates Gi/o G-protein which allows K+ efflux and interacts with Ca2+ ICs to prevent Ca2+ influx
both mechanisms result in hyperpolarisation where the membrane potential is more negative, inhibiting the generation and firing of an action potential
structure of a GABA-A ionotropic receptor?
pentameric assembly of 5 subunits with a central ion channel core
can be made up of different subunit types - alpha, beta, gamma and others like epsilon and theta
most common configuration is 2 alpha, 2 beta and one gamma
where are GABA-A receptors located?
on post-synaptic neurones
structure of a GABA-B metabotropic receptor?
GCPR, 7 transmembrane domains, C terminal which allows two receptors to link together and form dimers