Module 10 - Neurotransmitters Flashcards by Damari Martin

Receptor: what are they and what do they do?

Proteins that bind ligands and cause transduction to occur

How well did you know this?

Not at all

Perfectly

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

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)

How well did you know this?

Not at all

Perfectly

Ligands: what are they?

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

How well did you know this?

Not at all

Perfectly

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

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

How well did you know this?

Not at all

Perfectly

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

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

How well did you know this?

Not at all

Perfectly

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

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

How well did you know this?

Not at all

Perfectly

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?

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)

How well did you know this?

Not at all

Perfectly

The four parts of activating a GPCR

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

How well did you know this?

Not at all

Perfectly

The GPCR activation cycle

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

How well did you know this?

Not at all

Perfectly

Types of GPCR α-subunits

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

How well did you know this?

Not at all

Perfectly

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

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

How well did you know this?

Not at all

Perfectly

Types of neurotransmitters

Monoamines
Amines
Neuropeptides
Amino acids
Others

How well did you know this?

Not at all

Perfectly

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

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

Dopamine, serotonin, adrenaline, noradrenaline, and histamines

How well did you know this?

Not at all

Perfectly

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

Similar to monoamines but with a larger scope

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

How well did you know this?

Not at all

Perfectly

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

Small peptides chopped up from larger proteins

Substance P, endorphins, enkephalins, vasopressin, oxytocin

How well did you know this?

Not at all

Perfectly

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

Amino acids

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

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

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

NO, adenosine, ATP

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

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

Neurotransmitter criteria

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

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

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

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

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

Three different neurotransmitter systems

Acetylcholine receptors

Glutamate receptors

GABA receptors

Acetylcholine receptors: what are the two types

Nicotinic
Muscarinic

Acetylcholine receptors: nicotinic receptors

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

Acetylcholine receptors: muscarinic receptors

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

The key use of nicotinic and muscarinic receptors

Nicotinic - causes an AP to be fired when activated Muscarinic - Causes an AP to be fired if stimulated twice Allows for ACh receptor flexibility

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

Glutamate is significant in learning and memory Ionotropic (fast) and metabotropic (slow) are two types

Glutamate receptors: ionotropic receptors

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

Glutamate receptors: metabotropic receptors

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

Magnesium and its blocking in NMDA receptors

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

GABA receptors

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

Autoreceptors

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

Heteroreceptors

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

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

Usually means that it targets nicotinic acetylcholine receptors

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?

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)