Ligand gated channels

Question 1

What is important to note about stimuli and receptors such as extracellular ligands?

Answer 1

Most extracellular ligands dont enter the cell! They activate ligands. This can cause a cascade such seen with G proteins or these can alter the shape of the receptors.

Question 2

How many families of the receptor mammalian genome are there? And what do members of the same family have?

Answer 2

There are 25 families of receptor proteins
16 of them evolved to detect stimuli

Members of each family share one or more structurally homologous domains

These may be ligand binding domains or signal transducing domains

Question 3

What is the main function of ion channels?

Answer 3

Regulate membrane potential across a cell

Question 4

Types of ion channels? And calciums roles?

Answer 4

Ligand gated or voltage gated

Calcium can act as a second messenger remember. May affect membrane potential ect

Question 5

What is the very basic ion channel structure?

Answer 5

Two transmembrane domains to make up one protein

These domains anchor proteins in the plasma membrane

3 proteins make up an ion channel

Important to note - each protein in this instance has two transmembrane domains.

They have pores which form down the middle of the channel helping for ion absorption

Question 6

Potassium selective channels?

Answer 6

This is a primordial very old channel

Its made up of 4 proteins

These proteins have two transmembrane domains to make up one protein

Question 7

Important to note about potassium selective channels which have 4 proteins and 2 transmembrane domains?

In ref to the domains

Answer 7

Their transmembrane domains have p loops, which is a helical structures

There are also two OTHER helical domains in the transmembrane domains called s5 and s6

Question 8

The primordial channel: is a…

Answer 8

Very common type of channel

With 4 proteins

2 transmembrane domains to make up a protein

Each with a p loop

Question 9

What do adding extra transmembrane domains to the transmembrane domains on the typical primordial channels allow?

Answer 9

Allow for regulatory elements to be added to the channels

Question 10

What might different transmembrane domains do to charges of the ion channel?

Answer 10

Different transmembrane domains can cause proteins in the transmembrane domain to have positively charged amino acids.

These may enable for detection of voltage changes

Question 11

What does the amino terminus as a transmembrane domain allow for?

Answer 11

Allows for ligand detection

The transmembrane mostly spans the intracellular membrane of the ER

However it has an extracellular part which goes into the cytosol for ligand detection

Question 12

Features of a pentameric protein channel?

Answer 12

This is when the ion channel has 5 transmembrane domains

In this cases they have 4 proteins

Their transmembrane domains dont have a p loop

This type of channel is used by GABA and acetylcholine

Question 13

P loop structure and features?. Remember this is on the primordial channels transmembrane domains

Answer 13

These p loops come into close contact with other proteins. As in proteins in the ion channel

They affects the pores of the channels, they make up very small pores in the ion channels

Only small dehydrated potassium ions can fit into these gaps

This is a physical filter for only potassium ions

Question 14

What are potassium ions surrounded by outside of potassium channels?

Answer 14

They’re surrounded by water

Question 15

What happens when potassium ions bind to their channels?

Answer 15

It generates energy

This energy causes the channel to open

The ions line up in single file ass they enter the channel

Question 16

What happens when ions entering a channel are next to each other?

Answer 16

The ions repel each other

Each potassium ions repels the ion infront of it. This keeps the ions flowing through the channels

Question 17

What is typical about p loops and transmembrane domains in general?

Answer 17

They are often squished together - so they are relatively closed, stopping ions from moving in.

We need energy to be transduced.

Question 18

How do voltage gated channels sense voltage?

Answer 18

They have voltage gated domains

Question 19

How does depolarisation cause ion channels to open?

Answer 19

When the transmembrane domains which are voltage sensitive senses a change in voltage, it causes the transmembrane domains to pull open the channels.

This is regulation.

Question 20

What sub units may voltage gated channels have?

Answer 20

They may have alpha and beta sub units

The beta subunits may add extra components to these voltage gated proteins.

Question 21

What are inactivation peptides?

Answer 21

Part of the alpha sub units of some protein channels

After the channel is opened this peptide can enter the channel through the pore

This plugs the pore and is used to stop further flux of ions through it.

Question 22

How can you identify if a channel has less selectivity?

Answer 22

Their channels have bigger pores

Question 23

The cyclic nucleotide gated channel?

Answer 23

Tends to have 4 sub units

3 of those sub units must be simultaneously occupied

If a chemical then leaves there isnt the energy to keep the channels

Question 24

Describe the p2x receptor:

Answer 24

It has a primordial simple structure

Their receptors are gated by ATP - sensing ATP outside of the cell

You need 3 protein sub units to form a channel

The assemblies of the proteins can be homomeric or heteromeric

You mainly get 3 identical proteins coming together who have a pore down then. The binding of 3 ATP makes this channel open.

Question 25

Describe the glutamate receptor family: their shape, how many proteins are needed. How many transmembrane domains make up each protein, what’s important about the amine terminus?

Answer 25

The receptor family is a tetrameric receptor family

They are made up of 4 proteins, each protein is made of 2 transmembrane domains

Each set of transmembrane domains has a p loop

These receptors have very extended amine terminus’s which contain glutamate binding sites.

The glutamate binding site is folded.

Question 26

What is the clamshell model of the glutamate receptor?

Answer 26

When glutamate binds to the glutamate receptors cleft, it causes the shell to close ( a structure away from the pore)

The closing action around the glutamate molecule (away from the pore) gives the conformational change for the pore to be pulled open.

Question 27

The glutamate receptor dimer structure?

Answer 27

The receptor is made up of two sets of dimer. Two genes form one dimer and two form the other. The dimer is basically one protein.

There are two copies of the protein to make the receptor.

Question 28

What does the glutamate receptor let through

Answer 28

Sodium ions

However in some instances can also be permeable to calcium

Question 29

NMDA receptors? And what is significant of strokes?

These are a type of glutamate receptor

Answer 29

These are very permeable to calcium ions as opposed to AMPA receptors

When a person has a stroke, there’s alot of glutamate in the brain

This causes lot of the NMDA receptors to open and to let calcium out causing a build up of calcium in cells.

This causes the cell to die.

The receptors are also useful for memory and learning. But overuse leads to cytotoxicity.

Question 30

What classic structure does the nicotinic receptor have? What controls their selectivity? What are they permeable to?

Answer 30

These have a pentameric structure?

They are made up of 5 proteins

Each protein is made of 4 transmembrane domains

Their selectivity is controlled by the nature of the amino acids that line the pore.

Depending on those amino acids, the channels are permeable mainly to sodium and potassium and either permeable to calcium.

Question 31

Alterations in some of the nicotinic receptors amino acids can change the channel from being cation selective to anion selective.

What does this mean?

Answer 31

They may let chloride ions through instead of the usual potassium, sodium, calcium.

The channels which are chloride selective can hyperpolarise cells.

Question 32

What type of neurotransmitters are GABA and glycine neurotransmitters? And what do they make the receptors they bind to do due to slight changes?

Answer 32

These are inhibitory neurotransmitters

Glycine binds to receptors like the NMDA receptor

They work through channels with similar overall profiles

The changes to the GABA and glycine receptors cause:

Slightly higher changes in the pore region make them selective for chlorides.

Question 33

How do pentameric receptor channels open? How many alpha sub units must they have? What is found on the alpha sub units which isnt found on the beta sub units?

Remember the GABA and glycine receptors are nicotinic and have pentameric receptors

Answer 33

These channels become open due to twisting

Their transmembrane domains move relative to each other, the twisting causes the pore to open

These pentameric receptors must have two alpha sub units because these contain the ligand binding sites.

Note the beta and gamma sub units dont have a ligand binding site.

Question 34

Cis loop pentameric receptors? What causes the different pentameric receptors in the brain?

Answer 34

In pentameric receptors there are cystine bridges

The different sub unit combinations of pentameric receptors means pentameric receptors in the brain are different to each other in different parts of the brain

Question 35

Give one example of a nicotinic receptor in the brain which is involved in reward and nicotine addictions in the brain:

Answer 35

The nAchR (alpha)4 in the brain

Nicotinic acteyl choline receptor.

Question 36

What is special about the pentameric receptor channels in muscles?

Answer 36

They have different compositions to the pentameric receptors in the brain, because they must be close calcium stores

Whereas pentameric receptors in the brain don’t have to be

Question 37

Mutations in nictonic receptors may cause?

Answer 37

Epilepsy