Cholinergic synapses

Question 1

Two types of cholinergic receptor

Answer 1

nicotinic and muscarinic

Question 2

Structure of nicotinic receptor

Answer 2

Pentameric protein

two alpha, one beta, sigma and gamma

Binding sites for ACh in alpha chain

Three hydrophobic subunits M1-M3

each subunit has four hydrophobic segments

Question 3

Binding site structure

Answer 3

Two binding sites

Formed of two cysteine residues bound by disulfide bridges, containing 13 amino acids between them.

Contained in a cleft formed by a beta barrel

Question 4

Structure of selectivity filter + how it moves out the way

Answer 4

Large hydrophobic leucine residue in the centre.

When ACh binds, conformational change causes the M2 segment to rotate out the way so the cations can flow

Question 5

Structure of pore

Answer 5

Contain hydrophobic residues and several serine or threonine residues near the middle .

Contain a ring of glutamate and aspartate (anions) that help attract positively charged ions.

Filled with water

Question 6

What is the molecular weight of the channel?

Answer 6

290kDa

Question 7

Function of nACHr

Answer 7

Responds to binding of acetylcholine or nicotine, allows cations to flow through and thus depolarises the membrane/muscle

Question 8

Two subtypes of nACHr

Answer 8

muscle type N1 and neuronal, ganglionic type N2

Question 9

What is receptor desensitisation?

Answer 9

agonist is bound for a very long period of time, which induces a permanent conformational change in the receptor, so that it is no longer as complementary to ACh

Question 10

what drug can cause it + why?

Answer 10

Suxamethonium, as it has a longer duration of action than ACh, and is not hydrolysed by acetylcholineterase - instead by plasma cholinesterase

Question 11

Where is acetylcholine a neurotransmitter?

Answer 11

All autonomic ganglia, parasympathetically innervated organs, NMJ and many sites in CNS

Question 12

how many times does each nAChR subunit span the membrane?

Answer 12

4 times, so both N and C terminals are extracellular

Question 13

Structure of muscarinic receptor

Answer 13

• 7 hydrophobic membrane crossing segments
• alpha helix
• G protein coupled receptor- formed of three subunits, alpha, beta and gamma
• GDP bound tightly to alpha

Question 14

agonists of muscarinic receptors

Answer 14

muscarine and acetylcholine

Question 15

Muscarinic receptor function

Answer 15

• ligand, acetylcholine, binds to the binding site
• causes GTP to bind to the alpha subunit, causing it to detach
• alpha subunit then acts as a second messenger, initiating processes such as the activating adenyl cyclase to form cAMP or the inositol pathway.

Question 16

Different sub types

Answer 16

M1-M5

Question 17

How do the subtypes vary?

Answer 17

Vary in the G protein they are bound to- either Gs, Gi, Gq, or Go

Question 18

What G protein is attached to each sub type? + ROUGH FUNCTION

Answer 18

M1, M3 and M5 - Gq - stimulate inositol pathway and the release of intracellular calcium

Gi/o - M2 and M4- inhibit adenyl cyclase

Question 19

Location of each sub type

Answer 19

M1- postganglionic nerve

M2- heart

M3- smooth muscle in blood vessels

M4- CNS

M5- not well known

Question 20

Where is muscarine found?

Answer 20

Mushrooms

Question 21

Antagonist to muscarine

Answer 21

Atropine

Question 22

Explain atropine’s action

Answer 22

Competitive antagonist of the muscarinic acetylcholine receptors, thus blocks acetylcholine receptor sites, preventing the formation of action potentials

Binds to M2 receptor

Question 23

Atropine side effects

Answer 23

block contraction of circular pupillary sphincter muscle, opposes action of vagus nerve

Question 24

Why can ACh bind to both but N and M can’t?

Answer 24

acetylcholine is a flexible molecule

muscarine and nicotine are more rigid molecules

Question 25

Muscarinic receptor antagonist definition

Answer 25

Anticholinergic agent that blocks the activity of the muscarinic acetylcholine receptor.

Question 26

What causes an overactive bladder?

Answer 26

Detrusor overactivity

Question 27

What is a detrusor?

Answer 27

Smooth muscle found in the wall of the bladder which relaxes to store urine and contracts during urination to release urine.

Question 28

How can detrusor overactivity be prevented?

Answer 28

Use an antimuscarine, such as atropine, to prevent the stimulation of mAChRs so that the muscle no longer contracts as frequently

Question 29

What is asthma?

Answer 29

Long term inflammatory disease of the airways of the lungs characterised by reversible airflow obstruction and easily triggered bronchospasm. Increase in contraction of smooth muscle.

Question 30

Why are anticholinergics used?

Answer 30

ACh is released from cells lining the trachea, bind to airway mAChR which causes increased contraction of smooth muscle and mucus secretion.

All block mAChR- competitive antagonists

Question 31

What anticholinergics used?

Answer 31

Aclidinium, ipratropium and glycopyrronium.

Question 32

Two types of post synaptic potentials + explained

Answer 32

excitatory postsynaptic potential- EPSP- caused by rapid depolarisation as a result of the fast ion channel

Inhibitory postsynaptic potential -IPSP, less likely that an action potential will form.