Neurotransmitter receptors

Question 1

What are the two types of synapse?

Answer 1

Electrical - Electrical Synapses facilitate communication between neural cells: Ions move directly between neurons
Electrical synapses are in the minority

Chemical - At a Chemical Synapse chemicals known as neurotransmitters diffuse across the synaptic cleft from one neurone to another
Chemical Synapses constitute the vast majority of synapses

Question 2

What proved the importance of releasing chemicals?

Answer 2

Experiment from 1926
Heartbeat slowed when stimulated the vagus nerve of the heart, therefore the inhibitory effect of the vagus was transferred
The vagus releases chemicals to stimulate the heart (neurotransmitter)

Question 3

What main features are involved in a signal?

Answer 3

Neurotransmitters - responsible for transmission of signals between neurons
Neurotransmitter receptors - they detect the neurotransmitters, they are situated on the cell receiving the cell
There are ligand gated channels linked to the receptors

Question 4

What are the large groups of neurotransmitters?

Answer 4

Small molecules - they are synthesised by enzymes in the presynaptic neurone
Examples: amino acids (glutamate, GABA), Acetylcholine, ATP, biogenic amines (dopamine, noradrenaline), 5-Hydroxytryptamine (5-HT also known as serotonin), Endocannabinoids (lipids) and Nitric Oxide (NO)
Amino acids are the most important due to being monomers for proteins

Large molecules - encoded within the genome
Peptides

Question 5

Describe glutamate?

Answer 5

This is the major excitatory neurotransmitter
Over half of the synapses in the brain release glutamate
Generates EPSP
Too much Glutamate is toxic to neurones – excitotoxicity:
Ischemia, Epilepsy (seizures), Hypoglycemia and Trauma

Question 6

Describe the pathway of glutamate?

Answer 6

It is converted from glutamine by glutaminase
It is stored in a vesicle VGLUT
It is recieved by glutamate receptors at the post-synaptic terminal
It is resynthesized by being transported to a EATT transporter and converted back to glutamine by glutamine synthase in a glial cell
Then EATT helps the reuptake of glutamine back to the pre-synaptic terminal

Question 7

Describe GABA?

Answer 7

The major inhibitory neurotransmitter
About one third of the synapses in the brain release GABA
Generates IPSP which inhibits action potential firing (Cl-)

Potentiation of GABA signalling can reduce anxiety, be intoxicating:
Benzodiazepines (antidepressants, hypnotic), Barbiturates (Epilepsy) and Alcohol (intoxication and ataxia)

Question 8

Describe the pathway of GABA?

Answer 8

Derives from glucose -> glutamate -> GABA (the last link uses glutamic acid decarboxylase)
It is stored in vesicles VIATT
It binds to GABA receptors - they are ligand gated and allows Cl- to enter = more negative
It uses GAT transporters to reuptake into the presynaptic terminal

Question 9

What are catecholamines?

Answer 9

The molecules are characterised by having an amine on the side chain
Examples: Noradrenaline, adrenaline and L-DOPA (treatment for Parkinson’s disease)
Dopaminergic neurones in the substantia nigra degenerate in PD - dyskinesia

Question 10

In catecholamines give some examples of biogenic amines?

Answer 10

They are psychotropic drugs
Dopamine/5-HT involved in reward system
Antidepressants eg Prozac (5-HT reuptake block)
Cocaine (reuptake)
Ecstasy (vesicular transport)
Antipsychotic eg haloperidol, inhibits dopamine

Question 11

What are the peptide neurotransmitters? example?

Answer 11

They are larger molecules made from short strings of amino acids
Larger peptides are made as precursors:
Pre-propeptide -> propeptide -> active peptide -> active peptides

Modulatory peptides:
Substance P - associated with pain signalling
Which opioids inhibit substance P

Question 12

Where are modulatory peptides for pain eventually recieved in?

Answer 12

The dorsal root ganglion cell body in the spinal cord to the anterolateral system

Question 13

What is the co-release of neurotransmitters?

Answer 13

Low frequency - small-molecule neurotransmitter in smaller vesicles leads to a localised increase in Ca2+ concentration

High frequency - Release of both types of neurotransmitter (including neuropeptides from large dense core vesicles) leads to greater diffusion and increase in Ca2+ concentration

Question 14

How can a signal be terminated?

Answer 14

Inactivation of neurotransmitter eg acetylcholine using cholinesterase

Reuptake of neurotransmitter such as: glutamate, GABA, 5-HT and uses transporters on Glia and neurones

Diffusion away from synapse, using peptides but due to slow diffusion this is a longer lasting action

Question 15

What are the two classes of neurotransmitter receptors?

Answer 15

Ionotropic receptors - only bind to small molecule neurotransmitters
Act as part of the same molecular structure that forms an ion channel
Also called ligand-gated ion channel receptors

Metabotropic receptors - binds both small molecule and peptide neurotransmitters
Act through a second messengers that lead to metabolic changes in the cell
Also called G-protein coupled receptors because of the way they transmit the signal

Question 16

What is the structure of ionotropic receptors?

Answer 16

Made up of multiple interchangeable subunits which come together to form a central pore
Multiple ions pass through this pore (this is the ion channel)
The ion channel opens or closes in response to the neurotransmitters binding to the receptor

Question 17

What are the subunits of an ionotropic receptor?

Answer 17

Each subunit has an N-terminus domain in the extracellular space that binds the neurotransmitter
That N-terminus is linked to a number of transmembrane helices (either 3 or 4)
The helices react with other molecules in intracellular space (cytoplasm)
The subunits come together to form a an ion channel

Question 18

What is an example of a ionotropic receptor?

Answer 18

Nitcitonic acetylcholine receptor (nAChR)
There are five subunits that come together to form an nAChR receptor.
2 alpha subunits, 1 beta sub unit, 1 delta, and 1 gamma
The ion channel is permeable to Na+ and K+ and sometimes Ca2+
The opening is gated by the neurotransmitter

GABA
Permeable to Cl-
Other substances can bind at different sites to modulate receptor permeability

Question 19

Describe the pathway of an ionotropic receptor?

Answer 19

Binding of a neurotransmitter triggers the opening of an ion channel (they change shape when bound by a ligand)
This alters the concentration gradients of ions across the membrane
Leads to membrane depolarisation and therefore the generation of an action potential in postsynaptic cells
All of None response, either opened or closed which mediates rapid postsynaptic effect
An action potential is induced by glutamate receptors (excitatory)

Question 20

What is the structure of metabotropic receptors?

Answer 20

Monomeric structure
Seven transmembrane domains
Extra-cellular domain for neurotransmitter binding
Intra-cellular domain for binding G-proteins

Question 21

What are the subunits of metabotropic receptors?

Answer 21

Extra-cellular domain for neurotransmitter binding is made up from the transmembrane domains number 2,3,6 and 7
G-proteins bind to loop between transmembrane domains number 5 and 6, and to portions of the C-terminus

Question 22

Describe the pathway of a metabotropic receptor?

Answer 22

When a neurotransmitter binds to its receptor, the receptor activates G-protein (the receptor itself doesn’t have channels)
G-protein activates effector protein
Effector protein activates second messenger intracellular pathways
The ligand gates ion channel opens, allowing ions to flow across the membrane (but it’s not always a channel that will open as a result of a second messenger pathway)

Question 23

What are the potential effects of the metabotropic receptors?

Answer 23

Can amplify or dampen signals 
Mediate slow (potentially long lasting) effect in postsynaptic cells

Question 24

What are some second messenger pathways that are induced?

Answer 24

Noradrenaline - increases protein phosphorylation
Glutamate - increases protein phosphorylation and activates Ca2+-binding proteins
Glutamate (pathway 2) - decrease protein phosphorylation