Lecture 16: Acetylcholine and Amino Acid Neurotransmitters

What is the most common ways to classify neurotransmitters?

molecular make-up

examples of amines:

* dopamine
* norepinephrine
* epinephrine
* serotonin

What are some examples of amino acids:

* glutamate
* Gaba
* Glycine

Is acetylcholine an amine or amino acid?

Neither. It is its own thing

How many kinds of neurotransmitters do receptors respond to?

Most receptors only respond to one kind of NT

T'/F: Different types of receptors for the same NT will have different actions

True

What are the characteristics of Acetylcholine?

* main neurotransmitter within the skeletal nervous system
* The NT that has been the most studied

What is acetylcholine made of?

acetate and choline

What does acetyl CoA carry?

acetate

What does choline acetyltransferase do?

puts acetate and choline together

What does vesicular ACh transporter do?

moves the acetylcholine into the vesicles

What breaks up or inactivates acetylcholine?

Acetylcholine esterase

What happens to the breakdown products of acetylcholine?

products are taken up and reused

What are the two acetylcholine receptors?

* Nicotinic
* Muscarinic

What are the properties of the Nicotinic acetylcholine receptors?

* ionotropic
* nicotine binds to these receptors

What are the properties of the muscarinic acetylcholine receptors?

* Metabotropic
* most common type in the brain

What is Myasthenia gravis?

is a disease in which muscles are quickly fatigued with repetitive use

What does Myasthenia gravis target?

targets skeletal muscles, where the nicotinic ACh receptors are located

What kind of disease is Myasthenia gravis and why is that important?

This is an autoimmune disease. In this case, the patient’s own immune system attacks, or, in other patients, blocks, nicotinic ACh receptors at the NMJ

What is one treatment of Myasthenia gravis?

Removal of the thymus

What is alzheimers disease?

Alzheimer’s Disease is a slow-onset disorder that can start with mild forgetfulness but progresses to full-blown dementia, with patients’ often forgetting even their own family members

What is Alzheimer’s Disease is often associated with?

amyloid plaques and neurofibrillary tangles on postmortem examination

What is the correlation between acetylcholine and Alzheimers disease?

The degree of reduction of choline acetyltransferase (ChAT) activity in cerebral cholinergic neurons is significantly correlated with the severity of Alzheimer's disease

What has been found to be helpful in slowing down the progression of alzheimers?

Cholinesterase inhibitors

T/F: Alzheimers disease is directly correlated to an increase in acetylcholine

False. It is directly correlated to a decrease in acetylcholine

What will future therapies for alzheimers involve?

finding ways to increase ChAT activity

Do we know the cause of alzheimers? Why?

We don;t because there are other neurotransmitters involved in the progression of alzheimers besides acetylcholine

What other NT’s are involved in the progression or alzheimers besides acetylcholine?

Glutamate

T/F: It’s obvious how neurotransmitter activity should cause the histological abnormalities found with AD

False. It’t not obvious, hence why we haven’t discovered a cure

Why is acetylcholine considered its own thing?

Because its structure and functionality are completely different than amines and amino acids

Describe the neurobiology of myasthenia gravis

Ach has difficulty binding due to IgG blockage of the binding site. Ach rarely binds and Ach esterase begins to break it down

Where is glutamate found?

Is it inhibitory or excitatory?

pre synaptic or post synaptic?

* central nervous system
* excitatory
* posty synaptic

Where is GABA found?

Is it inhibitory or excitatory?

* in the brain
* inhibitory

Where is Glycene found?

Is it inhibitory or excitatory?

* spinal cord
* inhibitory

Do the three G amino acids normally act on ionotropic or metabotropic receptors?

ionotropic

Glutamate:

* How is it synthesized?
* How is it moved into vesicles?
* How is it removed from the synapse?

* synthesized from glutamine by glutaminase
* moved into vesicles by VGLUT
* Removed from synapse by excitatory amino acid transporters (EAAT’s) → glial cell cleanup

What are the three major types of glutamate receptors?

* AMPA
* NMDA
* Kainate

AMPA → what does it do and when is it active?

normal communication between cells and active anytime presynaptic cell is active

NMDA → When is it active and what is unique about it?

active during high levels of postsynaptic stimulation

* usually blocked by mg2+

How is the mg2+ removed from NMDA receptors?

during massive depolarization of both the presynaptic and postsynaptic cells

How is kainate activated?

kainic acid

Are the glutamate receptors selective or non-selective? What do they let in?

* non-selective
* allow Na+, K+, and Ca2+

GABA:

* How is it synthesized?
* How is it moved into vesicles?
* How is it removed from the synapse?

* synthesized from glutamate by glutamic acid decarboxylase (GAD)
* transported into vesicles by vesicular inhibitory amino acid transporter (VIATT)
* GAT’s: GABA transporters that inactivate GABA activity

How do you figure out if an NT is inhibitory?

it will turn glutamate into GABA

Glycine:

* How is it synthesized?
* How is it moved into vesicles?
* How is it removed from the synapse?
* What does it act on?

* synthesized from serine by serine hydroxymethyltransferase
* transported into vesicles via vesicular inhibitory amino acid transporter (VIATT)
* removed from the synapse by glycine transporters
* acts on ligand gated Cl- channels