Module 10 - Neurotransmitters Flashcards
Receptor: what are they and what do they do?
Proteins that bind ligands and cause transduction to occur
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)
Ligands: what are they?
Any class of neurotransmitter, drug, or hormone that binds to a receptor
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
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
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
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)
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
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
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
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
Types of neurotransmitters
- Monoamines
- Amines
- Neuropeptides
- Amino acids
- Others
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
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
Neuropeptides: what are they and what are their examples of them?
Small peptides chopped up from larger proteins
Substance P, endorphins, enkephalins, vasopressin, oxytocin
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)
