Neurotransmitters Flashcards
What is a feature of the metabotropic Neurotransmitter Receptor
It uses 2nd messengers to relay a signal intracellularly (Enzymatic reaction)
What are the two functions of 2nd messengers?
- To amplify a signal
2. To alter a signal
Give three examples of 2nd Messengers
- cAMP (nucleotide-based)
- diacylglycerol (lipid-based)
- Ions (Calcium)
What enzyme produces cAMP?
Adenylyl cyclase
Where can Acetylcholine be found?
It can be found at the neuromuscular junction - where a synapse meets the muscle cell
What different functions can Acetylcholine have?
- Relaxation of heart muscle cells
- Contraction of skeletal muscles
- Release of saliva from salivary glands
What two molecules is Acetylcholine made of?
Acetyl-CoA and Choline catalyzed by AchTransferae
What does VAChT (Vesicular ACh Transporter) do?
VAChT exchanges one molecule of Ach with 2H+ ions. The H+ ions are actively being loaded into the vesicle (ATP), so VAChT can exchange H+ for Ach
How is the signal neurotransmission of Ach terminated?
Ach is being broken down in the synaptic cleft by an enzyme called Ach-esterase
What part of ACh is being recycled after its breakdown?
The Choline part is being recycled
What are the names of the two types of ACh receptors?
- Nicotinic (ionotropic)
2. Muscarinic (metabotropic)
What ions flow through the Nicotinic ACh receptors?
Positive ions (mainly Na+)
What affects the differences between Nicotinic receptors in different parts of the body?
The subunit composition of those receptors affects many of its functions.
When is a G-protein active?
When its receptor is activated, bound GDP is being released and GTP binds to the site. The protein is then cleaved into an active alpha-subunit and beta/gamma-complex
What ACh receptors are found on the heart, skeletal muscles, and salivary glands?
- Muscarine 2 receptor on the heart (metabotropic)
- Nicotinic receptor on the skeletal muscle
- Muscarine 1 receptor on the salivary glands.
Name a few examples of toxins for ACh receptors
- Muscarine (Muscarinic receptor agonist)
- Nicotine (Nicotinic receptor agonist)
- alpha-bungarotoxin (Nicotinic antagonist)
- Curare (Nicotinic antagonist)
- Atropine (Muscarinic antagonist)
What is Glutamate made of?
Glutamate is made of Glutamine, catalyzed by Glutaminase
How is Glutamate being transported inside a vesicle?
It works in a similar way to ACh, where H+ ions are actively pumped inside the cell using ATP, and Glutamate is then exchanged by VGLUT (vesicular Glutamate Transporter) with the H+ ions inside the cell.
Why can’t glutamate be broken down in the synaptic cleft?
Because there is no enzyme to break down glutamate
How is Glutamate removed from the synaptic cleft?
Glutamate is being pumped out by Glial cells, then transformed into Glutamine, and transported back to the cell to be reused
What does EAAT stand for?
Excitatory Amino Acid Transporter (found on Glial cells - transports glutamate inside)
Why does glutamate have to be transported back to the presynaptic cell as glutamine?
Because if the unmetabolized glutamate is being released by the glial cell into the environment, it has the chance to excite the neurons needlessly - this is why it must be metabolized first
What are the names of Glutamate ionotropic receptors?
- AMPA
- NMDA
- Kainate
What is the name for the metabotropic Glutamate receptors?
mGluR (metabotropic glutamte receptor)
What is the function of Glutamate?
Glutamate mediates the excitatory input inside the brain
Describe some characteristics of the ionotropic Glutamate receptors
- AMPA has a very sharp and short action potential. It acts fast and closes fast
- NMDA is slower to react but closes slower as well. This gate lets in Ca2+ ions
- Kainate is not usually found in the brain
How can a Glutamate leak lead to toxicity and eventually death?
If glutamate spills in the environment, it will excite the receptors. Ca2+ will flow into the cell and prolonged calcium influx leads to cell death. (snowball effect)
What ion is important for blocking the NMDA ion channel?
Mg2+ blocks the entrance of NMDA. Because it is positively charged, it repels other positive ions like Ca2+, Na+, and K+ from passing through
What is the basic concept of Long-Term Potentiation?
By stimulating an NMDA receptor (in the hippocampus), the starting potential of a synapse will be higher so it will be excited more easily
Where the metabotropic receptors for Glutamate found and why?
They are found on the edge of the synapse and serve as a sensor for when “too much” Glutamate is released.
How does the negative feedback loop for Glutamate work?
There are metabotropic Glutamate receptors on the edges of both pre and post-synaptic cells. The receptors on the presynaptic cells tell the cell itself to not release more Glutamate if enough is already present in the synaptic cleft
What is the function of GABA?
GABA is driving all the inhibitory signals in the brain
How is GABA transported inside vesicles?
In a similar way like ACh and Glu - A vesicle is pumped with H+ and then VIAAT (GABA Transporter) is exchanging H+ with GABA molecules
How does GABA get pumped out of the synaptic cleft?
GABA does not have any enzymes that break it down, so it gets removed by the Glial cells and the presynaptic cell itself, with the transporter GAT
What are the names of the ionotropic GABA receptors?
GABA-A
What are the names of the metabotropic GABA receptors?
GABA-B
What anesthetics are used on GABA-A?
- Benzodiazepines (Valium)
- Barbiturates
- Alcohol
First three cause prolonged opening of GABA-A - Picrotoxin - This toxin blocks GABA-A and treats an overdose of the other anesthetics
What ions go through the GABA-A receptor?
Cl- ions
What does GABA-B do?
GABA-B suppresses the activity of other ion channels, so no signal can occur. This is done through several pathways (prevents depolarization)
What are the five Catecholamines?
- Dopamine
- Norepinephrine
- Epinephrine
- Serotonin
- Histamine
What is the metabolic pathway of (all) Catecholamines?
Tyrosine -> DOPA -> Dopamine -> NADR -> ADR
Where are catecholamines made?
They are made in special neurons in the brain. For example, Dopamine is made in the Substantia Nigra.
What does Prozac do?
Prozac prevents the reuptake of serotonin (unsure, more research neded)
Are there ionotropic and metabotropic receptors for Catecholamines?
No, there are only metabotropic receptors for catecholamines - however, only Serotonine has a ionotropic receptor
Where are Neuropeptides made?
In the ER of the neuron
Roughly explain the way of Neuropeptides from the nucleus to the synapse
The peptide is made in the ER through gene transcription and translation. The Pre-propeptide is then transported to the Golgi, where it is cleaved into a propeptide and packaged in a vesicle. There are also enzymes present in the vesicle that transform the propeptide into active peptides as it travels along the axon, to the synapse
What is an example of Neuropeptides?
Endorphins (opioid peptides)
What do endorphins do?
They block pain signals
What are examples of unconventional neurotransmitters?
- NO gas
- Endocannabinoids
They cannot be stored in a vesicle because they go easily through the membrane.
Why do endocannabinoids give a pleasurable feeling?
Many receptors for this compound are expressed in the substantia nigra, which in turn activates a reward feeling
