Lecture 6: Synaptic Transmission || (Neurotransmitters and Receptors) Flashcards
The excitability of neurons conferred by the expressions of ______ that allow ________ when activated
channels
depolarisation
If local potentials reach ________ for voltage-gated ______ channels, an _________ _________ is initiated
threshold
Na+
action potential
A local potential can be both _________ and _________
excitatory
inhibitory
_______ allows saltatory conduction along the axon
myelination
What are the three different types of neurotransmitters?
small molecules
neuropeptides
gaseous transmitters
Give two examples of small molecule neurotransmitters involved in classical neurotransmitters, and state whether they are excitatory or inhibitory
- glutamate: excitatory
- GABA: inhibitory
Most neurons in the brain have which types of neurotransmitters?
both neuropeptide neurotransmitters and small molecule neurotransmitters
ACh is a class of which type of neurotransmitter?
small molecule
What are some sites of action for ACh? (5)
brain, NMJ, autonomic endings, basal ganglia, GI tract
Amino acids are a class of which type of neurotransmitter?
small molceule
Give 3 examples of amino acid neurotransmitters
glutamate
GABA
glycine
What are three sites of action for amino acid neurotransmitters?
brain, spinal cord, retina
Biogenic amines are a class of what type of neurotransmitter?
small molecule
What are 3 examples of biogenic amine neurotransmitters?
adrenaline
noradrenaline
dopamine
What are three sites of action for amino acid neurotransmitters?
brain, spinal cord, sympathetic endings
Purines are a class of what types of neurotransmitter?
small molecule
What are two examples of purines as neurotransmitters?
ATP
Adenosine
What are two sites of action for purine neurotransmitters?
brain
autonomic ganglia
Peptides are a class of what type of neurotransmitter?
neuropeptides
What are three sites of action for neuropeptide transmitters?
brain, spinal cord, pituitary gland
Gasses are a class of what type of neurotransmitters?
gaseous neurotransmitters
Give two examples of gaseous neurotransmitters
Nitric oxide
carbon monoxide
What is the most common excitatory neurotransmitter in the brain?
glutamate
Do glial cells participate in synaptic transmission?
yes, astrocytes are active participants in synaptic transmission and are active in communication between neurons and the brain
How is glutamate synthesised in the pre-synaptic neuron?
glutamine is converted to glutamate via the enzyme glutaminase
What are the four stages of glutamatergic synapses?
- synthesis of glutamate
- packaging of glutamate
- exocytosis of glutamate
- recycling
Describe the packaging process of glutamate during glutamatergic synapses
the packaging of glutamate is energy dependent so it requires the activity of ATPase to power the vesicular glutamate transporter (vGLUT) glutamate to pump glutamate up its conc gradient into the vesicles (thus requiring the energy from ATPase to break down ATP)
Describe the process of exocytosis of glutamate during glutamatergic synapses
The action potential arrives, voltage gated Ca2+ open, Ca2+ influx which triggers vesicle fusion. This releases glutamate into the synaptic cleft. There is diffusion across the synaptic cleft to activate glutamate receptors on the post-synaptic cell
Describe the process of recycling of glutamate during glutamatergic synapses
The glial cells expresses excitatory amino acid transporters (EAAT) 1 and 2 which mops up any of the extra glutamate that gets released. This is converted back to glutamine via glutamine synthase and then pumped out of the astrocyte and back into the axon terminal by EAAT5
Describe the roll of EAATs
They pump glutamine of glutamate against their concentration gradient into astrocytes or neurons. This requires energy
Pumping glutamine or glutamate up their concentration gradient into astrocytes or neurons requires energy. Where does this energy come from?
it comes from the co-transport with things going down their concentration gradient (usually Na+)
Gaseous neurotransmitters act on receptors in the synaptic cleft BECAUSE gaseous neurotransmitters freely diffuse across the cell membrane
the first statement is false and the second statement is true
Why are drugs of abuse bad?
because they interact with systems in the brain and cause physical changes in the brain
Give an example of a drug of abuse and what it increases the levels of
methamphetamine
increases levels of noradrenaline, dopamine, serotonin
Meth stimulates what responses?
it stimulates fight, flight or fright response and stimulates the reward centres
Nicotine mimics the effect of which neurotransmitter?
ACh
PCP and ketamine mimic the effects of which neurotransmitter?
glutamate
Anti-anxiety drugs mimic the effect of which neurotransmitter?
GABA
Meth mimics the effect of which neurotransmitter?
adrenaline
Ecstasy mimics the effect of which neurotransmitter?
serotonin
Heroin mimics the effect of which neurotransmitter?
opioids
What are the two receptors in the post synaptic cells involved in classical neurotransmission?
ionotrophic and g-protein coupled receptors
What is the main receptor involved in neurotransmision?
g protein-coupled receptors
What are ionotrophic receptors?
they are the ones which are themselves an ion channel
the complex on which the transmitter binds is the same complex that has the channel within its structure
What are G-protein coupled receptors?
a type of metabotrophic receptors (things that change molecular signalling)
the G-protein is the start of a second messenger system within the target cell
What is the most common type of metabotrophic receptor?
G-protein coupled receptors
Describe how metabotrophic receptors work
the neurotransmitter binds to the cell surface receptor
the G protein complex inside of the cell which is attached to the receptor, once activated by the transmitter, the α subunit dissociates which does something to another protein
this could be activated of an ion channel
What three subunits make up the G protein complex inside the cell of a G protein coupled receptor?
α, β, gamma
Describe the process of activation of an ion channel by a G-protein coupled receptor
the α subunit dissociates which does something to another protein and in this case, it is the opening of an ion channel. Ions cross the membrane which changes the membrane potential for the cell (depolarisation or hyperpolarisation - excitatory or inhibitory)
What is the advantage of the second messenger system opening an ion channel?
you can have the same messenger which can have the opposite effect on the ion channel
Describe an ionotrophic receptor
the transmitter binds to a receptor where the ion channel is an integral part of the receptor
when the neurotransmitter binds, the ion channel opens which causes ions to flow either in or out of the cell, depending on the electrochemical gradient
Describe the glutamate receptor
is has three transmembrane domains and four subunits
depending on the combination of subunits, you can make different types of glutamate receptors as they confer different properties to the receptors
Give three subtypes of glutamate receptors
NMDA, AMPA and kainate receptors
What do the three subtypes of glutamate receptors have in common?
they all have the same ion channel so they are all excitatory
What type of receptor is a glutamate receptor?
an ionotrophic receptor
What are the types of ions what flow through glutamate receptors?
Na+, Ca2+
Cys-loop receptors are what type of receptor?
ionotrophic receptor
How many transmembrane domains are there in a cys-loop receptor?
4
How many subunits does a cys-loop receptor have?
5
Can you have different subclasses of cys-loop receptors by changing up the subunits involved?
yes
What ions flow in and out of a cys-loop receptor?
K+ flows out
Na+, Ca2+ and Cl- can flow in
How is NO produced in an axon terminal?
arginine is converted to citruline by nitric oxide synthase and NO is a byproduct
How does NO get from the presynaptic cell to the post-synaptic cell?
it diffuses
What is the effect of NO on the post0synaptic cell?
NO acts on soluble guanylyl cyclase which changes the activity of this enzyme to use energy to convert GTP to cGMP. This is a second messenger system
Why can NO go anywhere and have an effect in lots of places?
because it is lipophilic which means that it can diffuse across any cell’s membrane
