ACh

Question 1

What is ACh?

Answer 1

A very important neurotransmitter in both central and peripheral nervous systems

Question 2

What is it synthesised from?

Answer 2

Choline from the synaptic cleft or breakdown of phosphatidylcholine
Acetyl CoA from respiration
Enzyme = choline acetyletransferase

Question 3

How is ACh packaged for release?

Answer 3

Contained in clear vesicles, small amount free in cytoplasm
Vesicular ACh transporter is an antiporter which uses an efflux of protons to influx ACh
Stored in vesicles until AP generated

Question 4

Regulation of release

Answer 4

1. Arrival of action potential at synapse
2. Ca2+ channels open and therefore Ca2+ influx
3. Ca2+ encourages vesicles to move to and fuse with the plasma membrane, emptying their contents into the synaptic cleft
4. ACh binds to auto receptors on plasma membrane of pre-synaptic neurone to prevent subsequent ACh release

Question 5

Agents which interfere with ACh release

Answer 5

Botulinum toxin cleave SNARE proteins which administrate fusion of vesicles within the membrane

• Used clinical in botox and as a local anaesthetic
• Pathologically causes flaccid paralysis

Question 6

Termination of the neurotransmitter

Answer 6

• Reuptake occurs very quickly
  Na/Cl symporters used to import down the conc. gradient, exploiting the electrochemical gradient
• Degradation
  Acetylcholinesterase breaks the ester bond -> choline and acetate -> recycled during reuptake to reform ACh

Question 7

Important sites of parasympathetic innervation

Answer 7

Gonads 
Circular muscle of eyes 
Heart 
Intestines 
Bronchi

Question 8

Parasympathetic innervation of the heart

Answer 8

Decreased pacemaker activity
Decreased AVN conduction rate
Inhibits sympathetic nervous system

Question 9

Autonomic use of ACh

Answer 9

Sweat glands
Arrectores pilli muscles
Medulla of adrenal glands

Question 10

Muscarinic ACh receptor

Answer 10

M1 - Gq - secretory glands - activation
M2 - Gi - cardiac tissue - inhibition
M3 - Gq - lungs, exocrine glands, smooth muscle, pancreas - activation

Question 11

Activation of M2 muscarinic receptors

Answer 11

• Binding of ACh causes a conformational change in the G protein which causes it to split into alpha and beta-gamma subunits
• The alpha-i subunit inhibits the enzyme adenyl cyclase which decreases the second messenger cAMP which decreases protein kinase A
• This causes the opening of K+ channels and the closure of Ca2+ channels, decreasing heart rate