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Neurotransmitter systems

34 important questions on Neurotransmitter systems

What is special about metabotropic neurotransmitter receptors?

They have a 2nd messenger inside the cell that amplify the signal and trigger an intracellular response.

What types op intracellular responses can be triggered by 2nd messengers?

Protein phosphorylation
Gene transcription
Opening of ion channels

What are examples of 2nd messengers?

cAMP
Diacylglycerol
Calcium

Where is acetylcholine (mainly) released?

In the neuromuscular junction.

What transports acetylcholine into the vesicles?

Vesicular ACh transporter (VAChT)

How is the signal of acetylcholine terminated?

By acetylcholine breakdown via acetylcholine esterase

How does the vesicle acetylcholine transporter (VAChT) work?

It takes up H+ (protons) by using ATP. Then 2 protons are exchanged for 1 ACh.

What are the two different types of acetylcholine receptors? What is the difference?

Nicotinic ACh receptors and muscarinic ACh receptors
Nicotinic: ionotropic receptors. Upon binding of ACh, rotation along axis and opening of pore.
Muscarinic: metabotropic receptors. GPCR, activated α-unit and activated β/γ-unit upon ACh binding

What type of ACh receptor is present on the heart muscle and what is the effect when ACh binds?

Muscarinic AChR
Effect: decreased rate & force of contraction

What happens if you inject or inhale α-bungarotoxin or curare?

These are antagonists of the nicotinic receptors and cause paralysis.

What type of neurotransmitter is glutamate?

A simple amino acid, it is the on signal (excitatory input; depolarizes neurons).

How is glutamate transported into the vesicles?

Via vesicular glutamate transporters (VGLUTs). 1 proton is exchanged for 1 glu-.

How is the glutamate signal terminated?

By uptake into the glial cell and presynaptic terminal via excitatory amino acid transporters (EAAT).

What is the glutamate-glutamine cycle?

Glutamate is taken up into the glial cells here it is converted into glutamine via glutamine synthetase. It is released via SN1 and taken up into the presynaptic terminal via SAT2. In the presynaptic terminal glutamine is converted back into glutamate via glutaminase.

What are the different glutamate receptors?

Ionotropic receptors: AMPA, NMDA, Kainate
Metabotropic receptors (mGluRs)

What is special about NMDA receptors?

NMDA receptors are opened by glutamate and depolarization. Glutamate causes the conformational change but depolarization is needed to remove the Mg2+ molecule that is in the pore.
NMDA receptors are needed for LTP (long-term potentiation).

What is special about the mGluRs?

These are also present on the presynaptic side and cause negative feedback. They suppress the SNARE proteins, preventing fusion of the vesicles.

How can you get too much glutamate, what is this called and what happens? How can it stop?

Prolonged Ca influx activates the break down of lipid and proteins and induced apoptosis. All the components are then spilled out, glutamate activates more receptors that also go into apoptosis.
This is called excitotoxicity.
Glial cells can stop this effect by taking up the glutamate.

What type of neurotransmitter is GABA?

GABA is an inhibitory neurotransmitter, it mediates the off-signal.

How is GABA produced?

It is produced out of glutamate by glutamic acid decarboxylase & pyridoxal phosphate.

How is GABA transported into vesicles?

GABA is transported into vesicles via vesicular inhibitory amino acid transporter (VIAAT).

How is the signal of GABA terminated?

Transport into the glial cell via GABA transporter (GAT).

What is important to know about GABA-A receptors?

GABA-A are Cl- conducting ion channels, they suppress neuronal activity (because of hyperpolarization).
These receptors are often targets of anaesthetics.

What are bezodiazepines or barbiturates?

These cause a prolonged or more frequent opening of GABA-A, leading to more suppression of neuronal activity.

What is picrotoxin? When is this used?

Picrotoxin blocks GABA-A. This is used to treat overdose of barbiturates or benzodiazepines. It works like the Mg2+ in glutamate receptors.

Catecholamines can only be made by certain neurons in the brain. Where can noradrenaline be made?

Locus coeruleus

Catecholamines can only be made by certain neurons in the brain. Where can adrenaline be made?

In the medullary epinephrine neurons

What are the monoamine receptors?

Only metabotropic receptors because there is no on/off signal but modulation.

Monoamines have only metabotropic receptors. However there is 1 exception. What is this?

Serotonin has 1 ionotropic receptor: the serotonin prereceptor (located presynaptically).

What is special about neuropeptides?

Neuropeptides are made in the soma of neurons and travel along the axons. While it is travelling along the axon it is cleaved into the active peptide(s) by proteolytic cleavage.

What are unconventional neurotransmitters? Can you give two examples?

These neurotransmitters are membrane permeable and can therefore not be stored in vesicles. These are mainly used for feedback mechanisms.
Examples: endocannabinoids and NO

Where can endocannabinoids bind?

In substantia nigra (pleasure, reward)
In cerebellum (motor control)
In hippocampus (early formation of memory)

What is special about endocannabinoids (two things)?

Contain a tail of carbohydrates, which makes them lipophilic (and thus hard to store in vesicles).
We can make these ourselves out of lipids.

What is retrogade feedback?

From the target back to the original source.

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