Barbiturate/Diazepam - GABA signalling

Question 1

volume tranmission

Answer 1

intercellular communication –> occurs in CSF, movement via diffusion
slow transmission
e.g. dopamine

Question 2

GABAergic neurons

Answer 2

release GABA

Question 3

does GABA or glutamate have a chiral carbon

Answer 3

Glu

Question 4

GAD

Answer 4

glutamate decarboxylase

Question 5

role of glutamate decarboxylase

Answer 5

catalyses decarboxylation of glutamate to GABA

Question 6

2 forms of GAD

Answer 6

GAD65

GAD67

Question 7

where is GAD65 found

Answer 7

nerve terminals

Question 8

where is GAD 67 found

Answer 8

throughout cells

Question 9

GABA biosynthesis

Answer 9

GABA is made from glutamate

Question 10

transporters to get GABA into cells

Answer 10

GAT1

GAT3

Question 11

transporters to get GABA into vesicles

Answer 11

VGAT

Question 12

other use of VGAT

Answer 12

also puts Glycine into vesicles

Question 13

receptors activated by GABA

Answer 13

GABA A and GABA B receptors

Question 14

termination of GABA neurotransmitter action

Answer 14

diffusion

uptake by VGAT transporters

Question 15

ionotropic GABA receptor

Answer 15

GABA A

Question 16

metabotropic GABA R

Answer 16

GABA B

Question 17

properties of GABA A R

Answer 17

ionotropic
pentameric
cys loop on extracellular side
N and C terminals both extracellular
Cl- through central pore

Question 18

most common GABA A R structure

Answer 18

a1 B2 a1 y2 B2

Question 19

properties of GABA B R

Answer 19

metabotropic
7 TM domain
obligate dimer
N-terminus extracellular/C-terminus intracellular

linked to K+ channels via G-proteins

Question 20

GABA C

Answer 20

sub class of GABA A receptors
therefore also ionotropic
however
insensitive to GABA A antagonist bicucilline
less sensitive to GABAzine

Question 21

GABAzine

Answer 21

competitive antagonist

Question 22

ligands binding to orthosteric site

Answer 22

bind to GABA site

Question 23

muscimol

Answer 23

GABA agonist

psychoactive substance in mushrooms

Question 24

GABA competitive antagonists

Answer 24

bicucilline

GABAzine

Question 25

picrotoxin

Answer 25

non-competitive antagonist | pore blocker of GABA

Question 26

allosteric ligands

Answer 26

bind to a site alternative to GABA site | modulate signalling

Question 27

examples of GABA allosteric modulators

Answer 27

benzodiazepines alcohol neurosteroids barbiturates

Question 28

benzodiazepine site

Answer 28

between gamma and alpha 1 subunits

Question 29

effect of BDZ on GABA R

Answer 29

postivie allosteric modulator increases effect of GABA increases frequency of bursts of channel opening

Question 30

physiological effects of BDZ

Answer 30

reduce anxiety anticonvulsant promote sleep can be addictive

Question 31

effect of inverse agonists at GABA site

Answer 31

decreases effect of GABA | therfore seizures might be promoted

Question 32

competitive antagonist at BDZ-site

Answer 32

flumanezil

Question 33

property of BDZ-site ligands that makes them good for focussed therapeutic use

Answer 33

some of the ligands have different affinities and selectivity for GABA A receptor subtypes e.g. BDZ doesnt work on a6 subunits

Question 34

why can barbiturates/neurosteroids kill you at high dose

Answer 34

they directly activate receptors and cause respiratory failure

Question 35

effects of barbiturates

Answer 35

bind to different site to BDZ increase duration of bursts of channel opening positive allosteric modulator

Question 36

where do GABA A receptors clsuter

Answer 36

on the post synaptic membrane

Question 37

what causes GABA A R to cluster

Answer 37

intracellular proteins

Question 38

therapeutic uses of short/intermediate-acting barbiturates

Answer 38

sleeping pills | sedatives

Question 39

which GABA reeceptor has a slow IPSP and why

Answer 39

GABA B receptor | mediated by GIRK channels and K+ movement

Question 40

GIRK stands for

Answer 40

G-protein coupled Inwardly Rectifying K+ channel

Question 41

mechanism of baclofen to create an IPSP

Answer 41

hyperpolarises post-synaptic cells by increasing K+

Question 42

how does baclofen decrease neurotransmitter release from pre-synaptic

Answer 42

inhibits Ca2+ channels

Question 43

how does baclofen decrease cAMP production

Answer 43

inihbiits adenyl cyclase

Question 44

main function of baclofen

Answer 44

selective agonist of GABA B receptors | acts like Gi/o --> decreased cAMP and activates GIRK channels

Question 45

"plus side" of GABA A receptor

Answer 45

formed by TM2 and TM3 of the principal (upper) subunit

Question 46

'minus side' of GABA A receptor

Answer 46

formed by parts of TM1 and TM2 of the complementary subunit

Question 47

4 transmembrane domains of GABA A make up which two subunits

Answer 47

principal subunit | complementary subunit

Question 48

does the IPSP change size with successive action potentials

Answer 48

if 2 identical presynaptic stimuli are given in rapid succession, the 2nd IPSP will be smaller