Lecture 3 - Ion Channels

Question 1

What are the three types of ion channels?

Answer 1

1. Voltage gated
2. Neurotransmitter - gated
3. Second messenger-gated

Question 2

What is the function of voltage gated ion channels

Answer 2

The function of voltage gated ion channels is to allow for transient depolarisation (Membrane voltage changes during an action potential)
E.g.
* Na+ channels - Open and allow Na+ influx to make membrane voltage more positive
* K+ channels - Open to allow K+ efflux which drives membrane to more negative potential
* Ca2+ channels allow an influx of Ca2+ which increases cytosolic Ca2+ levels which is especially important at synapses where electrical signals are converted into calcium 2+ signals.

Question 3

What are neurtransmitter gated channels?

Answer 3

The gating of these channels are controlled by extracellular substances bind to the receptor/channel. This is commonly seen in the nervous system at synapses where neurotransmitters are released into the synaptic cleft and bind to receptors on the post synaptic cell. Depending on the neurotransmitter that binds this can have an excitatory (acetyl choline and glutamate) or an inhibitory effect (GABA and glycine).

Question 4

What are second messenger-gated channels?

Answer 4

The gating of these channels is by a cytosolic second messenger.
E.g. Cyclic nucleotide-gated channels (Cation-selective and gated by cAMP or cGMP) They are active in olfaction and enables detection of smells and also in photoreception to enable one to perceive light (vision).
E.g. Inositol 1, 4, 5 triphosphate (IP3) receptors - These are Ca2+ selective and release Ca2+ from the ER to elevate cytosolic Ca2+ during cell signalling events.
1. Pip2 is cleaved from Phospholipase C to form IP3
2. The IP3 diffuses before it reaches an Ip3 gated Ca2+ ion channel in the endoplasmic reticulum
3. This causes the channel to open and calcium to be released into the cytosol
The calcium then subsequently causes a downstream signalling event.

Question 5

Give examples of the structure function relationships of ion channels.

Answer 5

• Voltage gated ion channels are composed of 6 transmembrane spanning (TMS) domains and a pore domain. (S4) TMS is composed of positively charged side residues. There is a long N terminus which forms ball and chain arrangement involved in inactivation (different to deactivation when closed by voltage). Four of these monomers come together to form a tetramer.
  
  • Different channels will have different ammino acids that are found in the P domain
  • For example ion selectivity in K+ channels is due to the carbonyl oxygen of the glycine residues in the p-domain which means that the K+ must move through the pore in a dehydrated manor. Therefore sodium is unable to pass through as it has a higher charge density and therefore more energy is required to remove the water
  • K+ ion channels are multiple ion channels meaning more than one ion can move through at once. The positive charges of the ions moving through the channel repel each other driving the movement
  • Na+ channels are selective as Na+ passes through the narrow pore partially hydrated. K+ is unable to do this as it is too large to get close enough to Glu 117 to be dehydrated so it is unable to pass through.
  • Voltage channels are able to detect the change in voltage through the positively charged residues in the S4 TMS. The change in voltage forces the arginine residues to move up through the membrane which causes a conformational shape change opening the gate