OCB03-2008 ACETYLCHOLINE Flashcards
How is acetylcholine formed?
Formed from choline by choline acetyl transferase
How is the action of ACh terminated?
ACh hydrolysed by acetylcholinesterase on the postsynaptic membrane
Choline transported back into presynaptic neuron
What reaction is catalysed by acetylcholinesterase?
ACh –> acetate + choline
What are the two types of ACh receptor?
Nicotinic
Muscarinic
Describe a nicotinic ACh receptor. (3)
Ion channel
Pre and postsynaptic
5 subunits - 2α and 3β
Where are the ACh binding sites on a nAChR?
α subunits (2 sites)
How many types of α subunits are there that can form part of a nAChR?
8
What is the effect of activating a presynaptic nAChR?
Neurotransmitter release due to Ca++ influx
What is the effect of activating a postsynaptic nAChR?
Depolarisation to mediate fast excitation
What happens when a nAChR is activated?
Conformational change = pore opens
Na+, K+ and Ca++ enter cell
How many ACh molecules are required to activate a nAChR?
2
What is the structure of a nAChR common in the CNS?
(α4)2(β2)3
What are the nAChR responsible for in the CNS?
Addiction
Describe a muscarinic ACh receptor.
GPCR
Pre and postsynaptic
Enhances or inhibits target neuron activity
How many types of mAChR are there?
5
What G proteins are the mAChRs coupled to?
1, 3, 5 = Gq
2, 4 = Gi
What happens when the odd numbered mAChRs are activated?
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
What is PIP2 and what does it do?
Phosphatidyl inositol bisphosphate
Binds K channels to regulate activity; hydrolysis of PIP2 closes K channels
What does IP3 stand for?
Inositol triphosphate
What does DAG stand for?
Diacylglycerol
What happens when the even numbered mAChRs are activated?
Adenylyl cyclase inhibited
Close Ca channels or open K channels depending on location (inhibitory)
Where are cholinergic pathways found in the brain?
Basal forebrain to cortex, amygdala, hippocampus
Brainstem
Striatum (caudate nucleus/putamen)
Retina
What are the main responsibilities of the amygdala?
Memory
Decision-making
Emotions
What are the main responsibilities of the hippocampus?
Learning
Memory
How are cholinergic pathways implicated in Alzheimer’s disease?
Early reduction in basal forebrain fibres innervating the cortex
What can be used to treat Alzheimer’s disease?
Anti-cholinesterase drugs (increase ACh)
What type of drug is galantamine?
Anti-cholinesterase drug
What is the role of ACh in the brainstem?
Musculoskeletal and parasympathetic motor pathways from cranial nerve nuclei
Reticular activating system with pontine nucleus for arousal and consciousness
What is the role of ACh in the striatum (caudate nucleus/putamen)?
~1% are constantly active cholinergic interneurons which innervate the GABAergic medium spiny interneurons which output to the globus pallidus (proprioceptive movements)
What is the role of ACh in the retina?
Interneurons (eg amacrine cells)
How does ACh affect arousal/increased attention to sensory input?
Brainstem cholinergic neurons activate thalamic and cortical centres to increase arousal
How does ACh affect consciousness and REM sleep?
Acts with GABAergic system
M1 and M3 thought to be important in pattern of REM sleep
How does ACh affect motor control?
Regulates dopamine activity and release (mAChR)
What drugs can be used to treat tremor in early Parkinson’s disease (ACh)?
Muscarinic antagonists
How does ACh affect ingestive behaviour?
Interneurons and nucleus accumbens release ACh to influence food/other intake (may be involved in addiction)
Which AChRs contribute to learning and memory?
Muscarinic receptors
