Neurotransmitters Flashcards
Define a NT (4 points)
- Must be present in the presynaptic neuron
- Must be released in response to presynaptic depolarisation
- Release is usually Ca 2+ dependent
- Specific receptors must be present on post-synaptic cell
Mechanisms of post-synaptic excitation (cell is becoming more positive)
- Opening of Na channels
- Suppression of Cl and K channels
- EPS receptors increase in number and localisation
- Suppression of inhibitory receptors
Mechanisms of post-synaptic inhibition
- Increased Cl conductance
- Increased K conductance
- IPS receptors increase in number and localisation
- Inhibition of cellular metabolism (< metabotropic response)
What effect do Cl and K channels have on the potential of the cell?
Cl channels let Cl INTO the cell to keep it -ve, and K channels let K OUT to keep it -ve. The more of these channels are open the harder it will be for Na to create an AP. The more of these are closed the bigger the effect of Na
What is the NT ACh’s post-synaptic effect?
Excitatory
What are the precursors for ACh?
Choline and acetyl CoA
What is the removal mechanism for ACh?
AChEase (acetylcholinesterase)
Glutamate has an inhibitory post-synaptic effect. (T/F?)
FALSE- it is excitatory
What is the prescursor for glutamate?
Glutamine
What is the removal mechanism for glutamate?
Transporters
What is the most important excitatory NT in the brain?
Glutamate
What are the most important inhibitory NTs in the brain?
Gamma-aminobutyric acid (cerebrum) and glycine (spinal cord)
Gamma-amino butyric acid has an excitatory post-synaptic effect. (T/F?)
FALSE- it is inhibitory
What is the precursor for GABA?
Glutamate
What is the removal mechanism for GABA?
Transporters
What is the post-synaptic effect of glycine?
It is inhibitory
Serine is the precursor for glycine (T/F?)
TRUE
What is the removal mechanism for glycine?
Transporters
What chemicals does the term “catecholamines” include?
Ad, NAd and dopamine
What post-synaptic effect do catecholamines have?
Excitatory
Tyrosine is the precursor for catecholamines (T/F?)
TRUE
What are the removal mechanisms for catecholamines?
Transporters, MAO, COMT
What are MAO and COMT?
Enzymes involved in metabolising catecholamine neurotransmitters.
What is the systematic name of serotonin? (Abbr. 5-HT)
5- hydroxytryptamine
Serotonin has an excitatory post-synaptic effect (T/F?)
TRUE
What is the precursor for serotonin?
Tryptophan
What are the removal mechanisms for serotonin?
Transporters, MAO
What does MAO stand for?
Monoamine oxidase
The post-synaptic effect of histamine is inhibitory (T/F?)
FALSE- it is excitatory
What is the pre-cursor for histamine?
Histidine
What is the removal mechanism for histamine?
Transporters
What is the post-synaptic effect of ATP?
Excitatory
What is the precursor for ATP?
ADP
What is the removal mechanism for ATP?
Hydrolysis to AMP and adenosine
What type of neurotransmitter includes ACh, glutamate, GABA, glycine, catecholamines, serotonin, histamine and ATP?
Small molecular weight NTs
What are the post-synaptic effects of neuropeptides?
Excitatory and inhibitory
What are the precursors for neuropeptides?
AAs
What is the removal mechanism for neuropeptides?
Proteases
What is the post-synaptic effects of endocannabinoids?
Inhibits inhibition
What are the precursors for endocannabinoids?
Membrane lipids
What is the removal mechanism for endocannabinoids?
Hydrolysis
What are the post-synaptic effects of NO?
Excitatory and inhibitory
What is the precursor for NO?
Arginine
What is the removal mechanism for NO?
Spontaneous oxidation
Where are small molecule NTs synthesised?
In the nerve terminal
Small molecule NTs mediate very slow synaptic action (T/F?)
FALSE- they mediate rapid synaptic action
Where are neuropeptides synthesised?
In the cell body
What is the speed of synaptic action of neuropeptides compared to the small molecule NTs?
Neuropeptides have slower ongoing synaptic function
What is different about the degradation of small molecule NTs and neuropeptides once they a re released from the pre-synaptic membrane?
Small molecule NTs are broken down into their precursors which then diffuse back into the cell. Neuropeptides diffuse away from the terminal and are broken down by proteolytic enzymes.
What happens when there is a low frequency of stimulation of the nerve?
There is a localised increase in Ca concentration, which results in the preferential release of small molecule NTs.
What happens when there is a high frequency of stimulation of the nerve?
There is a more diffuse increase in Ca concentration, which results in the release of both types of NTs; small molecule NTs in small clear-core vesicles and neuropeptides in large dense core vesicles.
What effect does histamine have on the body?
Histamine results in a strong vasodilation, which results in a decrease in BP.
What is the difference between ionotropic and metabotropic receptors?
Ionotropic receptors are ligand-gated ion channels, and work very rapidly, about 0.1ms.
Metabotropic channels are G protein-coupled receptors, and are slower, taking about 400ms (in the heart).
All skeletal muscles are cholinergic in response and have direct cholinergic neurons innervating them. (T/F?)
TRUE
Dopamine is capable of activating both G-protein coupled (metabotropic) and ionotropic receptors. (T/F?)
FALSE- Dopamine acts EXCLUSIVELY by activating G-protein coupled (metabotropic) receptors.
What happens to excess dopamine?
It is deaminated by MAO in both the PRE and POST-synaptic membrane
What type of receptor are ALL of the histamine receptors?
G-protein linked
Of the three receptor types that are recognised for ATP, how many are G-protein linked?
Two- one is ionotropic
Only one neuropeptide can be released from a single vesicle. (T/F?)
FALSE- more than one NP may be released from a single vesicle
What makes a prepropeptide turn into a propeptide?
A prepropeptide has a signal sequence on the end, and once this is cleaved it becomes a propeptide.
Propeptides can give rise to more than one peptide NT. (T/F?)
TRUE
Nicotinic receptors are ionotropic ACh receptors (T/F?)
TRUE
How many subtypes of muscarinic receptors (mAChR) are there?
5
Where are the mAChR expressed?
the striatum and other forebrain regions.
These inhibit dopamine mediated motor effects
Glutamate can cross the B/B barrier. (T/F?)
FALSE- it must synthesised locally from mitochondrial conversion alpha-ketoglutarate (which comes from the CAC)
What does EAATs stand for?
Excitatory Amino Acid Transporters
What is the function of EAATs and where are they located?
They are located on the membranes on both neurons and glial cells. They mediate delivery and uptake of glutamine from glial cells to neurons
What is VGLUT and what is its function?
VGLUT is a vesicular glutamate transporter- which loads glutamate into neuronal vesicles
The NMDA (N-methyl-D-aspartate) is an ionotropic receptor at which glutamate is excitatory. (T/F?)
TRUE
Where is GABA most common?
Local circuit interneurons and cerebellum
GABA is removed from the synaptic cleft by specific transporters known as………?
GAT- GABA transporter
GABA is loaded into neuronal vesicles by which transporter?
VIATT- Vesicular Inhibitory Amino Acid Transporter
There are three types of GABA receptors, GABAa, GABAb and GABAc. Which two are ionotropic?
A and C
Which G protein links the GABAb receptor?
GI/O
The beta gamma subunit of the GABAb receptor blocks two Ca channels, and activates KIR3.1, which does what?
The opening of the KIR3.1 means K rushes in and brings the potential further away from the threshold. It causes hyperpolarisation of the post-synaptic membrane.
The glycine receptor is a gated channel, gated by which ion?
Cl-
NO is made by what enzyme?
NOS- NO synthase
NO had a rapid offset. What happens to it?
It is quickly oxidised or bound to Hb
How is NO modulated?
By regulating NOS function
NOS has different isoforms. (T/F?)
TRUE
NO is not limited to synapses, as it can diffuse between cells. (T/F?)
TRUE
