Ligand gated ion channels 1

Question 1

What are ligand-gated ion channels?

Answer 1

Multiple subunit proteins which form cation or anion channels.

Question 2

What are the channel properties of ligand-gated ion channels determined by?

Answer 2

Subunit composition.

Question 3

What does pentameric mean?

Answer 3

The receptor is made up of 5 different subunits.

Question 4

What are the three types of GABA receptor?

Answer 4

GABAa, GABAb and GABAc.

Question 5

What are the properties of GABAa channels?

Answer 5

It is a chloride ion channel, it’s agonist is GABA/muscimol, it’s antagonist is bicuculline and has an inhibitory cellular effect.

Question 6

What are the properties of GABAb channels?

Answer 6

They are GPCR K+/Ca++ channels, their agonist is GABA/baclofen, the antagonists are saclofen/CGPs and they have inhibitory cellular effects.

Question 7

What are the properties of GABAc receptors?

Answer 7

They are Cl- ion channels, their agonists are GABA/muscimol, their antagonists are TPMPA and they have inhibitory cellular effects.

Question 8

What subunits are GABAa receptors made up of?

Answer 8

Two beta, two alpha and a gamma.

Question 9

Where are the binding sites for GABAa receptors and how many are there?

Answer 9

Two - at the interface between alpha and beta subunits.

Question 10

What is a cys-loop?

Answer 10

An extracellular region where the ligand binds.

Question 11

Where do agonists bind?

Answer 11

At the N-terminal domain at the interface of alpha/beta subunits.

Question 12

What happens when agonists bind?

Answer 12

There is opening of ion-selective pores (anion).

Question 13

What conformational changes occur when ligands bind?

Answer 13

There is rotation of extracellular beta-sheets that are transmitted to the TM2 domain.

Question 14

Do both agonist sites needed to be occupied?

Answer 14

For the channel to fully open - yes. Agonist binding increases the probability of the channel opening, two molecules binding will open it further and enhance the probability of it being open.

Question 15

What is agonist affinity and efficacy altered by?

Answer 15

The alpha subunit.

Question 16

What determines the agonist binding and activation to a channel?

Answer 16

Relative permeability, pore size and the presence of charged groups lining the pore.

Question 17

What is different in the structure of the pore when it is open vs. closed?

Answer 17

The amino acid composition of pore is different in the activated vs. inactivated state.

Question 18

What influence does the presence of different amino acids at the pore have?

Answer 18

Influences the ability of channels to be selective for different ions.

Question 19

What action potentials do inhibitory synapses generate?

Answer 19

Inhibitory postsynaptic potentials (IPSPs).

Question 20

How can the equilibrium potential for an ion be calculated?

Answer 20

Using the Nernst equation.

Question 21

What are the two models of ligand binding/channel opening?

Answer 21

Induced fit model and the allosteric model.

Question 22

What is the induced fit model?

Answer 22

Binding of an agonist to the receptor causes a conformational change in the ligand-binding site area which then propagates to the pore region to cause an opening of the ion-conducting pore.

Question 23

What is the allosteric model?

Answer 23

The model depicting how the receptor is constantly undergoing spontaneous transitions between different conformations that confer different affinity for the ligand. The binding of an agonist stabilizes the channel in the open state.

Question 24

How is GABA removed from the synapse?

Answer 24

Uptake through GABA transporters.

Question 25

What are the four states in the kinetic model for GABAa receptors?

Answer 25

Closed (unbound), closed (bound), desensitized and open.

Question 26

What is desensitization of GABA receptors altered by?

Answer 26

Endogenous factors (Zn, phosphorylation) and pharmacological agents (e.g. BZ). The effect of subunit composition is not well established.

Question 27

How many different types of GABAa alpha subunits are there?

Answer 27

6

Question 28

Where are alpha1 subunits found?

Answer 28

Widespread distribution in teh cortex, cerebellum and hippocampus.

Question 29

Where are alpha 6 receptors found?

Answer 29

Only in the cerebellum.