W3: Ligand gated ion channels - nicotinic acetylcholine receptors

Give two functions of nicotinic ACh receptors

• mediate fast excitatory neurotransmission in vertebrate skeletal muscle

• expressed in the brain and mediate the effects of nicotine

What happens to channels at low concentrations of ACh?

channel openings are infrequent

What happens to channels at high concentrations of ACh?

multiple channels open at once and individual currents summate

Where were nicotinic acetylcholine receptors first purified from and how were they purified??

the electric ray Torpedo

• purified by alpha bungarotoxin from snake venom (affinity purification)

What was the observed structure of nicotinic acetylcholine receptors from the electric ray?

five subunits:

• 2x α

• 1x β

• 1x γ

• 1x δ

4 transmembrane helices (M1-M4)

• both N & C terminus are located extracellularly

Describe the structure of the helices and what that implies

all similar implying that they all evolved from a common ancestral protein

Where is the ligand binding site of nicotinic acetylcholine receptors?

formed by the N terminal region of the alpha subunits

How is permeability to cations mediated in nicotinic acetylcholine receptors?

conferred by the M2 region of each subunit, which form the linings of the ion pore

• rings of negatively charged amino acids (glutamic acid) adjacent to M2 attract cations to the pore

State 3 different types of nicotinic acetylcholine receptors and list their composition

• muscle type nAChRs (2α 1β 1γ 1δ)

• neuronal type nAChRs (2α 3β) - hetero-oligomeric

• neuronal type nAChRs (5α) - homo-oligomeric

Give an example of agonist at nicotinic acetylcholine receptors

nicotine

Give an example of antagonist at nicotinic acetylcholine receptors

curare