Discuss the structural diversity of the family of neurotransmitter-gated ion channels and the extent to which nicotinic acetylcholine receptors can be considered typical of this family of ion channels.

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Discuss the structural diversity of the family of neurotransmitter-gated ion channels and the extent to which nicotinic acetylcholine receptors can be considered typical of this family of ion channels.

• Introduction
o Introduce neurotransmitter gated ion channels
o How are they anchored? (RAMPS) How are they phosphorylated?
o Main structural points and mechanisms of activation (briefly) – how does ligand binding work?
o Detail the main LGIC and state number of subunits and main agonists/antagonists
o Cys loop structure gene families – discuss relationships between gene families of the main types of LGICs
o Nicotinic AChR – describe the receptor and main agonists, ions
• nAChR
o Describe the structure (using diagrams)
o How the channel opens
o How does this channel compare to the general structure of ligand gated ion channels
o Ion selectivity filters – how does switching these affect permeability and therefore diversity in the channel?
o Subunit composition diversity (developmental shifts)
• Other LGIC (use examples of different types of receptors and then state whether or not the same/similar thing happens to AChRs)
o Subunit composition diversity
o Intracellular domain interactions
o Ion channel permeation properties
o Channel activation, agonist/antagonist binding
o Allosteric Modulation of responses (PAMS?)
o How are receptors desensitized?
o Auxillary subunits
• Conclusion
o Re-state main structural points on which AChRs compare with other LGIC (they are obviously very typical) but you need to find examples where they have specific features too that other receptors do not have
• Useful papers:
o http://www.sciencedirect.com/science/article/pii/S0092867405800261/part/first-page-pdf – the full article, but for some reason only the first page link copies. Type up the name on pubmed to get the full thing
o http://www.ncbi.nlm.nih.gov/pubmed/?term=structural+diversity+of+neurotransmitter-gated+ion+channels
o http://www.ncbi.nlm.nih.gov/pubmed/12527802
o http://www.ncbi.nlm.nih.gov/pubmed/19481063
o http://www.ncbi.nlm.nih.gov/pubmed/9364611
o http://www.ncbi.nlm.nih.gov/pubmed/15649582
o http://www.sciencedirect.com/science/article/pii/S0959440X94902186
o http://link.springer.com/article/10.1007/PL00005051#page-1
o http://link.springer.com/chapter/10.1007%2F978-1-4419-6445-8_2
o http://www.tcdb.org/search/result.php?tc=1.A.9
o http://cshperspectives.cshlp.org/content/4/3/a009662.full