Debbi Hay 5

Question 1

What are the structural features of ligand gated ion channels?

Answer 1

Has a ligand binding site extracellularly which can introduce a conformational change causing opening and closing of the pore
Are multimeric (can be heteromers or homomers) and assembly of the subunits forms a central ion pore
The ligand binding sites are often a considerable distance from the gate
Ligand binding site is commonly located at an interface between two subunits as this is more energetically favourable as domain interfaces undergo larger conformational changes during ligand binding

Question 2

What are the three families of ligand gated ion channels?

Answer 2

Cys-loop
glutamate
ATP

Question 3

What are the structural features of Cys-loop ligand gated ion channels?

Answer 3

All subunits have a cys-loop (contain conserved cysteine residues which form a small loop of amino acids at the N terminus)
Subunits are 4 transmembrane domains with extracellular N and C termini
May be cation or anion channels
The gate is often in Transmembrane domain 2
There is extensive subunit diversity
They are Pentameric
Examples include nAChR and 5-HT

Question 4

What are the two types of receptor for acteylcholine?

Answer 4

nAChR which is a ligand gated ion channel
and a muscarinic receptor which is a GCPR
this allows for the lugand to have a wide range of diverse effects on the body with nAChR being important at the neuromuscular junction where it mediates signalling between nerve and muscle cells

Question 5

What are the structural features of nAChR?

Answer 5

There are many different subunits (17)
The neuromuscular junction type is 2 alpha1 units and one of beta1, gamma, delta units
Binding of Acetylcholine results in the opening of the pore allowing cation flow increasing the chance of an action potential

Question 6

What is the mechanism of action for nAChR?

Answer 6

ACh binding triggers a rotation of the transmembrane 2 helices by 15 degrees this moves the large bulky residues which usually occlude the pore replacing them with smaller residues allowing ion flow

Question 7

How is nAChR regulated?

Answer 7

The nAChR is broken down by acetylcholine esterases
The channel spontaneously converts to inactive state even with bound ligand
Receptor may be phosphorylated to reduce activity

Question 8

What are glutamate gated cation channels?

Answer 8

Cation channels responsible for most transmission in the brain

Question 9

What are the structural features of glutamate gated cation channels?

Answer 9

Large extracellular N-Terminal domain
They have three transmembrane domains with a re-entry P loop
The C terminus is intracellular
Part of the extracellular domain forms the ligand binding cleft enclosed by two lobes
Tetrameric
Four molecules of glutamate permit channel opening via a conformational change resulting from the binding cleft closing
The channel closes quickly despite the ligand still being bound representing the desensitized channel