OCB03-2008 ACETYLCHOLINE

Question 1

How is acetylcholine formed?

Answer 1

Formed from choline by choline acetyl transferase

Question 2

How is the action of ACh terminated?

Answer 2

ACh hydrolysed by acetylcholinesterase on the postsynaptic membrane

Choline transported back into presynaptic neuron

Question 3

What reaction is catalysed by acetylcholinesterase?

Answer 3

ACh –> acetate + choline

Question 4

What are the two types of ACh receptor?

Answer 4

Nicotinic

Muscarinic

Question 5

Describe a nicotinic ACh receptor. (3)

Answer 5

Ion channel

Pre and postsynaptic

5 subunits - 2α and 3β

Question 6

Where are the ACh binding sites on a nAChR?

Answer 6

α subunits (2 sites)

Question 7

How many types of α subunits are there that can form part of a nAChR?

Answer 7

8

Question 8

What is the effect of activating a presynaptic nAChR?

Answer 8

Neurotransmitter release due to Ca++ influx

Question 9

What is the effect of activating a postsynaptic nAChR?

Answer 9

Depolarisation to mediate fast excitation

Question 10

What happens when a nAChR is activated?

Answer 10

Conformational change = pore opens

Na+, K+ and Ca++ enter cell

Question 11

How many ACh molecules are required to activate a nAChR?

Answer 11

2

Question 12

What is the structure of a nAChR common in the CNS?

Answer 12

(α4)2(β2)3

Question 13

What are the nAChR responsible for in the CNS?

Answer 13

Addiction

Question 14

Describe a muscarinic ACh receptor.

Answer 14

GPCR

Pre and postsynaptic

Enhances or inhibits target neuron activity

Question 15

How many types of mAChR are there?

Answer 15

5

Question 16

What G proteins are the mAChRs coupled to?

Answer 16

1, 3, 5 = Gq

2, 4 = Gi

Question 17

What happens when the odd numbered mAChRs are activated?

Answer 17

Phospholipase C hydrolyses membrane-bound lipid (PIP2) to form IP3 and DAG

IP3 liberates Ca++ from intracellular stores

DAG activated protein kinase C to phosphorylate channels

Question 18

What is PIP2 and what does it do?

Answer 18

Phosphatidyl inositol bisphosphate

Binds K channels to regulate activity; hydrolysis of PIP2 closes K channels

Question 19

What does IP3 stand for?

Answer 19

Inositol triphosphate

Question 20

What does DAG stand for?

Answer 20

Diacylglycerol

Question 21

What happens when the even numbered mAChRs are activated?

Answer 21

Adenylyl cyclase inhibited

Close Ca channels or open K channels depending on location (inhibitory)

Question 22

Where are cholinergic pathways found in the brain?

Answer 22

Basal forebrain to cortex, amygdala, hippocampus

Brainstem

Striatum (caudate nucleus/putamen)

Retina

Question 23

What are the main responsibilities of the amygdala?

Answer 23

Memory

Decision-making

Emotions

Question 24

What are the main responsibilities of the hippocampus?

Answer 24

Learning

Memory

Question 25

How are cholinergic pathways implicated in Alzheimer's disease?

Answer 25

Early reduction in basal forebrain fibres innervating the cortex

Question 26

What can be used to treat Alzheimer's disease?

Answer 26

Anti-cholinesterase drugs (increase ACh)

Question 27

What type of drug is galantamine?

Answer 27

Anti-cholinesterase drug

Question 28

What is the role of ACh in the brainstem?

Answer 28

Musculoskeletal and parasympathetic motor pathways from cranial nerve nuclei Reticular activating system with pontine nucleus for arousal and consciousness

Question 29

What is the role of ACh in the striatum (caudate nucleus/putamen)?

Answer 29

~1% are constantly active cholinergic interneurons which innervate the GABAergic medium spiny interneurons which output to the globus pallidus (proprioceptive movements)

Question 30

What is the role of ACh in the retina?

Answer 30

Interneurons (eg amacrine cells)

Question 31

How does ACh affect arousal/increased attention to sensory input?

Answer 31

Brainstem cholinergic neurons activate thalamic and cortical centres to increase arousal

Question 32

How does ACh affect consciousness and REM sleep?

Answer 32

Acts with GABAergic system M1 and M3 thought to be important in pattern of REM sleep

Question 33

How does ACh affect motor control?

Answer 33

Regulates dopamine activity and release (mAChR)

Question 34

What drugs can be used to treat tremor in early Parkinson's disease (ACh)?

Answer 34

Muscarinic antagonists

Question 35

How does ACh affect ingestive behaviour?

Answer 35

Interneurons and nucleus accumbens release ACh to influence food/other intake (may be involved in addiction)

Question 36

Which AChRs contribute to learning and memory?

Answer 36

Muscarinic receptors