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Acetylcholine
Uni of Notts, Neurobiology of Disease, year 2, topic 10
| Term | Definition |
|---|---|
| Acetylcholine | The first discovered neurotransmitter; contracts muscles in the PNS and supports memory, attention, and learning in the CNS |
| Where AChR1-4 are located | Medial septal area, hippocampus, basal ganglia, & amygdala, supporting attention & memory |
| Where AChR5-6 are located | Brainstem (pedunculopontine and laterodorsal tegmental nuclei) involved in arousal & REM sleep |
| Where nAChR & mAChR are located in the PNS | Preganglionic nicotinic receptors & postganglionic muscarinic receptors stimulate or inhibit muscle tension |
| ACh synthesis & rate limiting step | Choline acetyltransferase forms an ester bond between acetyl‑CoA & choline. Choline reuptake limits synthesis, ~80% is recycled after hydrolysis |
| Quantity of ACh released per Action Potential (AP) | ~100,000 molecules per vesicle & ~300 vesicles per AP, 8-10x needed for motor‑endplate activation to ensure activation |
| Mechanism of organophosphate toxicity | Toxins such as VX & sarin inhibit acetylcholinesterase, causing sustained muscle contraction & potentially tetanus of respiratory muscles leading to asphyxiation |
| Nicotinic receptors | Ionotropic pentamers with at least two α‑subunits; always excitatory, involved in attention & reward in the CNS; preganglionic in the PNS |
| PNS nAChR subtypes | N1/Nm receptors at neuromuscular junctions & N2 receptors at autonomic ganglia |
| CNS nAChR component subunits | Combinations of a possible 9α & 3β subunits forming diverse receptor types. At least 2α needed to bind ACh |
| Muscarinic receptor subtypes | Five main subtypes (M1–M5), though structurally there are ~16 splice variants. M1-like (1, 3, 5) are excitatory & M2-like (2, 4) are inhibitory |
| Effects of progressive ACh depletion | Contributes to age‑related cognitive decline & worsens Alzheimer’s disease symptoms |
| Therapeutically enhancing ACh signalling | Using ACh agonists or reversible acetylcholinesterase inhibitors to improve cognitive function |
| How Alzheimer's is modelled in animals | Administering atropine, a muscarinic receptor antagonist, to impair cholinergic signalling |
| Experimental vigilance quantification task (+drugs that affected ACh receptors) | Participants detect repeated shapes; scopolamine impairs performance, nicotine improves it |
| Link between ACh & Schizophrenia | Mutations in the nicotinic α7 subunit increase risk; smoking alters nicotinic signalling & can worsen symptoms |
| Other disorders involving ACh | Autosomal Dominant Nocturnal Frontal Lobe Epilepsy (linked to nicotinic mutations) & altered mesolimbic dopamine via nicotinic receptor 5 |
Created by:
Denny12
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