Module 10 - Neurotransmitters

Question 1

Receptor: what are they and what do they do?

Answer 1

Proteins that bind ligands and cause transduction to occur

Question 2

Agonists: what are the types of agonists and what are the differences between them?

Answer 2

Full agonist - Fully activates a receptor, natural ligands will always be full agonists

Partial agonist - Partially activates a receptor, halfway between a full agonist and an antagonist (these are often drugs)

Question 3

Ligands: what are they?

Answer 3

Any class of neurotransmitter, drug, or hormone that binds to a receptor

Question 4

Cys loop receptors: what are they and what are examples of them?

Answer 4

Pentameric transmembrane receptors which are a type of ligand-gated ion channel that have at least two binding sites for ligands which activate the receptor

GABAA, nicotinic acetylcholine (nAChr), 5HT₃, and inhibitory glycine receptors

Question 5

Allosteric modulators: what are they and what do they do?

Answer 5

Binds to a site other than the receptor’s active site and either positively or negatively affects receptor activity

Question 6

Ligand-gated ion channels: what are they and what key features do they have?

Answer 6

Ion channels that open in response to ligand binding

• Pores which allow for ions to pass through
• Binding site allowing for ligands to bind
• Desensitization mechanisms - closing channels after being open for a set amount of time

Question 7

GPCR: what do they do, where are they located, how many are there in the human genome, what are examples, and what are the key characteristics?

Answer 7

G-protein coupled receptors act with paired proteins (G proteins) and use these proteins to influence cell activity via other proteins

Membrane - 7 transmembrane domain structure

The biggest family of receptors - 831 genes

β₂ adrenoreceptors

• Important in olfactory, vision, and nervous system
• Act via G-proteins (cAMP/IP3/PIP₂/PLC)

Question 8

The four parts of activating a GPCR

Answer 8

• An agonist ligand
• Membrane-bound GPCR
• G-protein (guanine nucleotide-binding protein) binds to a GTP/GDP as a trimeric membrane protein
• A protein (usually an enzyme) that acts as a secondary messenger

Question 9

The GPCR activation cycle

Answer 9

Step 1: A G-protein has a GDP attached to it

Step 2: An agonist binds to the GPCR, allowing the G-protein to attach and swap its GDP for a GTP

Step 3: The binding of GTP splits the G-protein into the α subunit with the GTP attached and the β and γ subunits

Both of these subunits will pass the message onto more target proteins

Step 4: The α subunit has GTPase so will eventually hydrolise GTP into GDP + Pi, resetting the signalling process

Question 10

Types of GPCR α-subunits

Answer 10

Gi proteins:
Gᵢ/α₀, αᵢ, α₀ - inhibition of adenyl cyclase (AC)
Gₜ, αₜ (transducin) - activation PDE 6 (vision)
G₉, α₉ᵤₛₜ (gustducin) - activation PDE-6 (taste)

Gs proteins:
Gₛ, αₛ - activation of AC
Gₒₗբ, αₒₗբ - activation of AC (olfaction)

Gq proteins:
Gq, αq - activation of phospholipase C

Question 11

The 6 most important transmitters and whether they interact with LGIC or GPCRs (plus a couple more significant transmitters)

Answer 11

ACh - Both (metabotropic and ionotropic)
Noradrenaline - GPCR only (metabotropic only)
Dopamine - GPCR only
Serotonin - Both
Glutamate - Both
GABA - Both

Glycine - LGIC only (ionotropic only)
Adrenaline - GPCR only
Neuropeptides - GPCR only
Histamine - GPCR only
Adenosine - GPCR only
ATP - both

Question 12

Types of neurotransmitters

Answer 12

• Monoamines
• Amines
• Neuropeptides
• Amino acids
• Others

Question 13

Monoamines: what are they and what are their examples of them?

Answer 13

Neurotransmitters derived from aromatic amino acids (Tyr, Trp, His) which should realistically be referred to as aromatic NTs

Dopamine, serotonin, adrenaline, noradrenaline, and histamines

Question 14

Amines: what are they and what are their examples of them?

Answer 14

Similar to monoamines but with a larger scope

ACh contains one amine group but contains lipids and is not aromatic

Question 15

Neuropeptides: what are they and what are their examples of them?

Answer 15

Small peptides chopped up from larger proteins

Substance P, endorphins, enkephalins, vasopressin, oxytocin

Question 16

Amino acids: what are they and what are their examples of them?

Answer 16

Amino acids

L-glutamate (excitatory in the brain), gamma-aminobutyric acid (GABA) (inhibitory in the brain), glycine (both in the spinal cord)

Question 17

Others: what are they and what are their examples of them?

Answer 17

The other NTS that do not exactly fit into any of the other classifications

NO, adenosine, ATP

Question 18

Dale’s principle: what is it, what is the difference with the original, and how accurate is it?

Answer 18

That a neuron will always release the same combination of NTs at every synapse

One neuron will only release one NT at every synapse - incorrect

This is a strong rule of thumb but there are exceptiions

Question 19

Neurotransmitter criteria

Answer 19

A neurotransmitter must:

• Be synthesised by the neuron
• Be present in the synaptic terminal at sufficient concentrations
• Be released on (pre)synaptic transmission
• Evoke a response on an exogenous application on a postsynaptic neuron
• Have mechanisms for its removal from the synaptic cleft

Question 20

Cholinergic terminal: what must happen to ACh after being released and what is the process for ACh breakdown?

Answer 20

After ACh passes the synaptic cleft and evokes a response in the postsynaptic neuron, it must be broken down

It is broken down by AChE which breaks ACh into acetate and choline and, while acetate is moved into surrounding tissue, choline is recycled into the cell where it interacts with choline acetyltransferase which reacts choline with acetyl-CoA to form acetylcholine and CoA

Question 21

The three ways that L-glutamate is removed from the synapse

Answer 21

1 - Excitatory amino acid transporters (EAAT) directly reuptaking and recycling L-glutamate

2 - Direct diffusion into the ‘soup’ surrounding the neuron (not ideal, way 3 is therefore present)

3 - Surrounding astrocytes containing EAAT take glutamate in and convert it into the inert glutamine using glutamine synthase which can be transferred easily back into the presynaptic neuron where it can be turned back into glutamate

Question 22

Three different neurotransmitter systems

Answer 22

Acetylcholine receptors

Glutamate receptors

GABA receptors

Question 23

Acetylcholine receptors: what are the two types

Answer 23

Nicotinic
Muscarinic

Question 24

Acetylcholine receptors: nicotinic receptors

Answer 24

Pentameric LGICs that are excitatory, enable fast transmission (μs-ms), contain a built-in cation channel and 16 subunits (in humans) that can combine in a wide number of receptors

Question 25

Acetylcholine receptors: muscarinic receptors

Answer 25

Monomeric 7 subunit transmembrane GPCRs which are both excitatory and inhibitory, enable slow transmission (ms-s), influence K⁺ permeability, and form 5 receptor types

Question 26

The key use of nicotinic and muscarinic receptors

Answer 26

Nicotinic - causes an AP to be fired when activated
Muscarinic - Causes an AP to be fired if stimulated twice

Allows for ACh receptor flexibility

Question 27

Glutamate receptors: what does glutamate do and what are the two types?

Answer 27

Glutamate is significant in learning and memory

Ionotropic (fast) and metabotropic (slow) are two types

Question 28

Glutamate receptors: ionotropic receptors

Answer 28

Three types of receptors:
* AMPA ()
* Kainate ()
* NMDA (permeable to Ca²⁺, blocked at Mg²⁺ at resting membrane potential,need glycione/D-serine as a coagonist)

Question 29

Glutamate receptors: metabotropic receptors

Answer 29

Three groups of receptors:
* 1 - mGluR₁, mGluR₅ (postsynaptic, excitatory)
* 2 - mGluR₂, mGluR₃ (presynaptic, inhibitory)
* 3 - mGluR₄, mGluR₆₋₈ (presynaptic, inhibitory)

Question 30

Magnesium and its blocking in NMDA receptors

Answer 30

At RMP, Mg²⁺ blocks the channel and prevents ionic movement; however, at -30mV the Mg²⁺ is removed and the channel restores its functionality

Question 31

GABA receptors

Answer 31

Basically the exact same as the last two except the metabotropic receptors inhibit Ca²⁺ channels and open K⁺ channels (reducing postsynaptic excitability), and inhibit adenyl cyclase

Question 32

Autoreceptors

Answer 32

Receptors for the neurotransmitter released by the nerve terminal in whose membrane they reside and when activated, these receptors regulate the release of that neurotransmitter - usually negative feedback

Question 33

Heteroreceptors

Answer 33

Whereas an autoreceptor responds to the neurotransmitter released by the neurone whose membrane it is embedded in, a heteroreceptor responds to a different neurotransmitter

Question 34

The meaning of alpha (α) at the front of a toxin name

Answer 34

Usually means that it targets nicotinic acetylcholine receptors

Question 35

Lynx 1: what is it, what does it do in the brain, how have the Lynx proteins evolved in elapid snakes, and what toxin examples are there?

Answer 35

A soluble protein regulator of neuronal nicotinic receptors, very important in brain development

In hollow-fanged (elapid) snakes, proteins related to Lynx 1 have evolved to become toxins which target muscle nicotinic acetylcholine receptors

Examples include α-cobra toxin and α-bungarotoxin (from the cobra and Taiwanese banded krait respectively)