GABA, Glutamate and their receptors

Question 0

what are metabotropic receptors ?

Answer 0

coupled to G protein - open or close ion channels via intermediaries
slower response
transduce signal to the cell interior - indirectly activate ion channels on the plasma membrane through signalling cascade which involved G proteins

Question 1

what are ionotropic receptors?

Answer 1

ligand gated ion channels
rapid response
depolarise or hyperpolarise the post synaptic cell- depends on receptor type and ionic gradient

Question 2

what is glutamate ?

Answer 2

most abundant excitatory neurotransmitter in the vertebrae nervous system

Question 3

what is GABA?

Answer 3

most abundant inhibitory neurotransmitter in the vertebrate nervous system

Question 4

when glutamate and is present in the synaptic cleft where does it go to be removed ?

Answer 4

enters glial cells or astrocytes or presynaptic terminal

Question 5

what enzyme converts glutamate to glutamine ?

Answer 5

glutamine synthetase

glutamine can be taken from glial cells into neurons

Question 6

if too much glutamate is present what can it cause ?

Answer 6

excitotoxicity
it can be highly toxic

a low concentration of glutamate applied to neurons in culture kills the cells

Question 7

what was discovered in the 1970s about glutamate ?

Answer 7

glutamate given orally produces neurodegeneration in vivo

- this caused considerable alarm because of the widespread use of glutamate as a taste enhancing food additive MSG

Question 8

what is excitotoxcity associate with ?

Answer 8

activation of NMDA receptors

• results mainly from a sustained rise in intracellular calcium concentration
• there are mechanism that act normally to protect neurones- calcium transport system

Question 9

what are the glutamate receptors like ?

Answer 9

metabotropic ones - mGluRs 1-8
- slow and modulatory

ionotropic ones

• AMPA, Kainate and NMDA - receptors are named after the agonists that bind to them with high specificity
• fast synaptic transmission

Question 10

what are the subunits of NMDA receptors ?

Answer 10

NR1
NR2A, B, C and D
NR3A and B

Question 11

what are the subunits of AMPA receptors?

Answer 11

GluR1
GluR2
GluR3
GluR4

Question 12

what are the subunits of Kainate receptors ?

Answer 12

GluR5 
GluR6 
GluR7 
KA1
KA2

Question 13

what are the classes of metabotropic glutamate receptors ?

Answer 13

class1 - mGluR1 and mGluR5 
class2- mGluR2 and mGluR3 
class 3 - mGluR4, mGluR6, mGluR7 and mGluR8

Question 14

what effects does activation of class 1 glutamate receptors have ?

Answer 14

stimulates phospholipase c
PIP2 is cleaved into DAG and IP3

they are activated by trans-ACPD and quisqualate

Question 15

what happens when class 2 glutamate metabotropic receptors are activated ?

Answer 15

inhibit adenylyl cyclase

activated by trans-ACPD and quisqualate

Question 16

what happens when the class 3 glutamate metabotropic receptors are activated ?

Answer 16

inhibit adenylyl cyclase
activated by L-AP4 and L-SOP
no effect caused by trans-ACPD and quisqualte so they can be differentiated from the class 2 receptors
act ass autoreceptors

Question 17

what is the obligatory subunit of NMDA receptors ?

Answer 17

NR1

if its not present then the channel cannot function

Question 18

what binds to the NR1 subunit of NMDA receptors ?

Answer 18

glycine
it doesnt actually activate the channel because it is a co agonist however it causes greater activation when glutamate binds

Question 19

what is PCP and what does it bind to ?

Answer 19

angel dust

binds to NMDA receptors

Question 20

what are the rules of assembly of AMPA receptors ?

Answer 20

• homomultimers= 2 or more identical components

- heteromultimers= 2 or more different components

Question 21

what are the rules of assembly of kainate receptors ?

Answer 21

GluR 5, 6 and 7 are homomultimers

heteromultimers

Question 22

what are the rules of assembly of NMDA receptors ?

Answer 22

heteromultimers
NR1 must partner 1 or more NR2 subunits
assemble as hetero-tetramers of 2 obligatory NR1 subunits and 2 regionally localissed NR2 subunits

Question 23

what are the modulatory sites of NMDA receptors ?

Answer 23

glycine binding sites
polyamine antagonist site
Mg 2+ block
channel blocking drugs

Question 24

what drugs target glutamate receptors ?

Answer 24

ketamine PCP AMPAkines

Question 25

what percentage of synapses does GABA localise to ?

Answer 25

30%

Question 26

what drugs are GABAa receptors sensitive and insensitive to and what are the effects of its activation ?

Answer 26

sensitive to BICUCULLINE insensitive to BACLOFEN activation causes chloride influx to hyperpolarize the cell

Question 27

what drugs are GABAb receptors sensitive and insensitive to and what are the consequences of its activation ?

Answer 27

sensitive to BACLOFEN insensitive to BICUCULLINE modulates neurotransmitter release via potassium ad calcium channels

Question 28

where is the GABA binding site in GABAa receptors?

Answer 28

between the alpha and beta subunits

Question 29

where is the benzodiazepine binding site in the GABAa receptors ?

Answer 29

between the alpha and gamma subunits

Question 30

where is the alpha 1 subunit of GABAa receptors present ?

Answer 30

widely distributed throughout brain

Question 31

where are the alpha2 subunits of GABAa receptors present ?

Answer 31

mainly present in the hippocampus

Question 32

where are alpha 3 subunits of GABAa receptors present ?

Answer 32

mostly in the cortex- none in the cerebellum

Question 33

where are the alpha 4 subunits of the GABAa receptors present ?

Answer 33

some in the hippocampus | low level expression throughout the brain

Question 34

where are the alpha 5 subunits of the GABAa receptors present ?

Answer 34

present in CA1 and CA3 regions in the hippocampus

Question 35

where are the alpha 6 subunits of the GABAa receptors present ?

Answer 35

100% in cerebellum - not present anywhere else

Question 36

what effect does GABA subunit composition have ?

Answer 36

it determines the intrinsic properties of the channel- affinity, kinetics, conductance, allosteric modulation, probability of channel opening, interaction with modulatory proteins and subcellular distribution

Question 37

what is the typical in vivo subunit composition of GABAa receptors ?

Answer 37

2 alpha, 2 beta and one gamma or delta subunit