LIGAND GATED CHANNELS

Question 1

What is the function of signalling systems in biology?

Answer 1

To recognise stimuli, transfer the stimulus into the cell, amplify the cytoplasmic signal, modulate the effector systems over time andadapt the system through feedback.

Question 2

In multicellular organisms, selective expression of certain receptors and the molecules involved in signal transduction allows cells to what?

Answer 2

Respond specifically to particular stimuli.

Question 3

Physical interaction of a stimulus with a receptor provides energy to change the structure of the receptor in such a way that what?

Answer 3

May initiate signalling.

Question 4

What detects membrane permeable stimuli?

Answer 4

Intracellular receptors.

Question 5

There are how many families of receptor proteins in the genome?

Answer 5

25

Question 6

Members of each family of receptor proteins share what?

Answer 6

One or more structurally homologous domains, whether that be a ligand binding domain and/or a signal transducing domain.

Question 7

What is the chemical signal generated by ion channels?

Answer 7

Change in ion composition of the cell.

Question 8

Key features of ion channels include:

Answer 8

Ion selectivity - specific or broad

Gating mechanism - ligand or voltage

Question 9

Evolutionary simple organisms had channels. Duplication of the gene coding for 2 TMSD domain channels gave rise to what?

Answer 9

A family of channels with 2-24 transmembrane spanning domains. Mutations in the TM4 gave rise to voltage sensitivity.

Question 10

Subunits of a ligand gated ion channel come together to form what?

Answer 10

A pore

Question 11

Between two transmembrane domains of many ligand gated ion channels are p loops. When subunits come together, what do these form?

Answer 11

A highly selective filter.

Question 12

On the cytoplasmic side, what creates the ‘gate’ that blocks a ligand gated ion channel.

Answer 12

The transmembrane domain tightly packed together.

Question 13

What happens to ions as they pass through a channel?

Answer 13

Ions must lose their hydration to fit through the filter. They then move in single file. The electrostatic repulsion of multiple ions near each other propels them through the pore down their electrochemical gradient.

Question 14

What is the significance of the KcsA (Kir) Primordial Bacterial Channel?

Answer 14

Was the first ion channel to be visualised.
The 2TM channel is conserved across many families. So the pore and tetrameric structure will remain the same across many families. With extra TMSD come more complex channels and their regulatory elements.
Others are thought to have evolved separately such as Cys Loop Ligand Gated Ion Channels which are pentameric and have no p loop.
Eg nAChR, GABAa

Question 15

What is the structure of a voltage potassium channel?

Answer 15

6TMSD
Tetrameric
Pore made up of S5 and S6 with a p loop.
TMSD 4 is positively charged and detects voltage.
Also has an inactivation peptide.

Question 16

What is the structure of a cyclic nucleotide gated channel?

Answer 16

6 TMSD
Tetramer
S5 + S6 make the pore
P loop controls filter (less selective)
Has a calmodulin binding site
Cyclic nucleotide binding domain detects cAMP + cGMP
3/4 sites must be filled for the channel to open

Question 17

What is the structure of the P2X receptor?

Answer 17

2 TMSD
Timeric
ATP binds to pockets on the extracellular surface

Question 18

What is the structure of an Ionotropic Glutamate Receptor?

Answer 18

4TMSD
Tetrameric (dimer of dimers)
Extracellular amino terminal for channel assembly.
Selective to Na/K
When glutamate binds in its cleft, it closes like a clam shell pulling on TM domains to pull the channel open.

Question 19

Na/K selective channels control membrane excitability and therefore what?

Answer 19

Depolarise cells.

Question 20

Cl selective channels control membrane excitability and therefore what?

Answer 20

Hyperpolarised cells.

Question 21

What are examples of a glutamate receptor?

Answer 21

NMDA

AMPA

Question 22

What is NMDA also selective to?

Answer 22

Calcium

Question 23

Why is overstimulation of NMDA receptors dangerous?

Answer 23

Toxicity - neuron death.

Question 24

What is the structure of Cys Loop Channels?

Answer 24

4 TMSD
Pentameric assembly
No p loop
Amino acid pore can change positive ion selectivity to negative ion selectivity.
Binding of nACh cause the subunits to rotate opening the pore.
Must have 2 alpha subunits where the ligand binding site is.
Eg nACH, GABAa

Question 25

There are multiple subunits that exist within any one ligand gated ion channel family. What is the advantage of this?

Answer 25

Complexity provides diversity and opportunity for drug targetting.

Question 26

Voltage gated ion channel and ligand gated ion channels work together to do what?

Answer 26

Control the excitability and function of muscle and neurons.

Question 27

Autoimmune induced loss of muscle nACHR causes what disease?

Answer 27

Myasthenia gravis

Question 28

Mutations in nACHR subunits can cause what?

Answer 28

A genetically transmissible form of epilepsy that is associated with a mutation in CHRNA4.

Question 29

Glutamate receptor signalling is known to regulate what?

Answer 29

LTP required for memory function.