7.4 Functional Aspects Of Excitation And Inhibition

Question 1

What are the receptor, activity, speed, action and clinical aspects of ionotropic receptors?

Answer 1

Ligand gated ion channel

Excitatory or inhibitory

Question 2

What are the receptor, activity, speed, action and clinical aspects of metabotropic receptors

Answer 2

7-TM receptor coupled G protein receptor
Activity dependent on signalling pathway
>100m- minutes (slow)
Action - amplification and interaction with other NTs
Clinical - agonists often abused as drugs

Question 3

What is unique about G protein coupled receptors

Answer 3

They allow for amplification

Question 4

What are the 5 steps of transmission?

Answer 4

Synthesis: pre synaptic requiring specific enzymes
Storage: pre synaptic, requires vesicular transport proteins
Release: into synoptic cleft via exocytosis or a constitutive pathway
Binding: concentration dependent, to Jono or metabotropic receptors
Termination: dependent on transmitter type and extra cellular space

Question 5

What are the receptor, activity, speed, action and clinical aspects of ionotropic receptors

Answer 5

Ligand gated channels

Excitatory or inhibitory

Question 6

What is the excitatory NT in the brain?

Answer 6

Glutamate

Question 7

What kind of receptors does glutamate work on?

Answer 7

Ionotropic and metabotropic

Question 8

What is the general mechanism of glutamate from vesicle to reuptake

Answer 8

Glutamate released, binds to post synaptic receptor, remaining glutamate uptaken by the glial cell, converted by glutamate synthase into glutamine, transported back into the presynaptic terminal of the neuron, converted by phosphate activated glutaminase into glutamate and packaged into vesicles

There is also some diffusion back into the presynaptic terminal via plasma membrane transporter

Question 9

What is the structure of the NMDA receptor?

Answer 9

4 subunits with 2 glutamate binding sites, blocked by Mg, glycine binding site

Question 10

What needs to happen for the NMDA receptor to open?

Answer 10

Need sufficient glycine in CSF, extrasynpatic receptors L-serine and need sufficient depolaisation to remove the Mg

Question 11

What happens with NMDA and AMPA receptors during excitation?

Answer 11

Glutamate is released from the pre-synaptic terminal, binds to AMPA and NMDA. NMDA receptor is blocked by Mg. Na enters through AMPA receptor causing slight depolarisation which removes Mg from its binding site on NMDA. This allows calcium to enter causing further depolarisation and synaptic activity.

Question 12

What is the antagonist for NMDA?

Answer 12

Ketamine

Question 13

What is the structure of the AMPA receptor?

Answer 13

4 subunits with 2 glutamate binding sites

Question 14

What is AMPA permeable to?

Answer 14

Na, K and some Ca

Question 15

What is the speed of AMPA and NMDA activity?

Answer 15

AMPA fast

NMDA slow

Question 16

Where would you find the Glu2 receptors of AMPA?

Answer 16

Present on the heterodimers of synapses onto excitatory cells

Question 17

What are the roles of the AMPA subunits?

Answer 17

GluR1: inserted during synapse formation in an activity dependent way
GluR2: responsible for constitutive recycling

Question 18

What are TRAPs and what are their role and what are they thought to be implicated in?

Answer 18

Transmemrabe AMPAR regulatory proteins
Modulate the AMPAR activity by regulating the trafficking of the receptors
Thought to be implicated in epilepsy and neurodegeneration

Question 19

What are Kainate receptors and what are their role?

Answer 19

4 subunits with 2 binding sits for glutamate, control of presynaptic release/inhibition
Agonist = kainic acid which causes epileptis seizures

Question 20

What is the location of the metabotropic glutamate receptors?

Answer 20

Perisyaptic

Question 21

What G proteins do Group 1, 2 and 3 metabotropic gluatamate receptors activate?

Answer 21

1: activates PLC - can be excitatory or inhibitory

2 an 3: Inhibits adenylate cyclase and prevents cAMP formation causing reduced activity of postsynaptic potentials

Question 22

What happens with too much glutamate?

Answer 22

When there is too much glutamate present there will be an influx of calcium causing excitotoxicity (neuronal damage and cell death)

Overexictation can cause epilepsy

Question 23

What is the major inhibitory NT in the brain?

Answer 23

GABA

Question 24

What is the GABA cycle?

Answer 24

Glutamine taken up into the neuron, converted to glutamate by glutaminase, metabolised into GABA by glutamate decarboxylase,. GABA is taken back up by diffusion into the neuron or into the glial cell where it is converted into glutamate and glutamine to be taken back up into the neuron

Question 25

What is the structure of the GABAa receptor

Answer 25

5 subunits with 2 binding sites for GABA
6 gene: B (3) and Gamma (3) in a 2:2 relationship
most common is 2a2b2gamma

Question 26

What is the GABAa receptor permeable to?

Answer 26

Cl, HCO3

Question 27

What are the agonists and antagonists for GABA receptors?

Answer 27

Agonist: muscimol
Antagonist: picrotoxin, bicuculline, gabazine

Question 28

What is the action of GABA?

Answer 28

Fast inhibition in the CNS

Question 29

What drug acts at the GABAa receptor?

Answer 29

Benzodiazepines

Question 30

What is angelman syndrome?

Answer 30

Loss of B3 GABA subunit

Question 31

What is the role of GABAb receptors?

Answer 31

pre and post synaptic inhibition, role in absence seizures

Question 32

When are agonists and antagonists of the GABAb receptor used?

Answer 32

Ag: spinal spasticity, dystonia and some types of neuropathic pain, gastroesophageal reflux

Ant: experimental use in cognitive decline, drug addiction and anxiety