L7 Cholinergics

Question 1

ACh synthesis

Answer 1

Choline is taken up into ACh synthesizing neurons by a Choline transporter
Enzyme-Choline acetyltransferase converts choline into acetylcholine
Transported into synaptic vesicles, vesicle in synapse-burst of ACh

Question 2

Regulation of ACh Release & regulation

Answer 2

Action potential runs down into the nerve terminal
Depolarising effect
Ca release acting as a cue for the synaptic vesicle to fuse with the neuronal membrane then it release its contents into the synaptic cleft

Question 3

ACh receptor

Answer 3

-ligand gated ion channels receptor family
-5 subunits that form a mature nicotinic receptor with an ion channel down the core of it
Skeletal muscle one standard form->
CNS-variety of nicotinic receptors, different alpha and beta subunits

Question 4

Nicotinic Receptor signaling

Answer 4

The agonist Interacts with the alpha subunit,
when binding occurs there is a conformation change in the nicotinic receptor, allows ions eg Na to enter down electrochemical gradient into the cell to cause depolarization

When ion channels open up, it exposes rings of negatively charged amino acids in the cell which is responsible for drawing positively charged ions into the cell
Electrostatic attraction to draw in positively charged ions

Initial depolarisation, reaches a certain level voltage gated channels open-> action potential

Question 5

Botulinum Toxin

Answer 5

Is specifically taken into ACh releasing neurons
Once its inside its cleaved into its active component
One of the active component of Botulinum Toxin has proteolytic activity and can cleave certain protein substrates

Enzyme that has the ability to chop up proteins-preferred protein to chop up are snare molecules which mediate the interaction between the synaptic vesicle and the neuronal membrane
No snare proteins-> no fusion of synaptic vesicle-> no exocytosis-> paralysis of the skeletal muscle (botox)

Question 6

How does AChE enhance the concentration and longevity of ACh in the synaptic vesicle

Answer 6

Blocking AChE enhances the concentration and longevity of ACh in the synaptic vesicle
Amplification of ACh’s effects thus enhancing cholingeric actions

Question 7

Described the M3 pathway

Answer 7

Smooth muscle, glands
Gq-> phospholipase C -> PIP2 -> IP3- increase in Ca-> GIT contraction /
vasoconstriction

DAG-> PKC activation

Question 8

Described the M2 pathway

Answer 8

Cardiac

Gq-> AC-> cAMP-> increase in Ca-> reduce force of cardiac contraction

Question 9

Effects of Botulinum Toxin on Ach vesicle exocytosis

Answer 9

Synaptic vesicle containing ACh and upon depolarisation of the nerve terminal and the entrance of Ca, synaptic vesicle has a protein on its membrane- its a lipid constrained synaptic vesicle,
Proteins can interact with complementary proteins found on the inner surface of the neuronal membrane
When the interaction comes the snare proteins draws on the lipid membrane of the synaptic vesicle in alignment with the lipid membrane of the neuronal cell-> permits exocytosis of the synaptic vesicle