MR 5

Question 1

Describe some aspects of the diversity of calcium channels.

Answer 1

There are many different types that are located in different places.
They can be blocked or activated by different agents so that there is a local effect.
They are structurally similar to the Na channels.
There are different types, eg L-type, R-type…

Question 2

How does the neurotransmitter get released at a junction? Make reference to calcium.

Answer 2

Depolarisation causes an increase in [ca2+]i
The Ca2+ binds to synaptotagmin, which brings the vesicle containing the neurotransmitter to the surface.
A snare complex makes a fusion pore, through which the neurotransmitter is released.

Question 3

What are the names of 2 methods of blocking nicotinic receptors?

Answer 3

1. Competitive

2. Depolarising.

Question 4

Outline competitive blocking nicotinic receptors. Give an example of such a molecule.

Answer 4

Tubocurarine.

Binds competitively at the nAchR. This competes with ACh. Can overcome this by giving more ACh as you are just simply increasing the concentration of the true ligand.

Question 5

Outline the method of depolarising agents at nicotinic receptors. Give an example of such a molecule.

Answer 5

Succinylcholine.

Initially causes a depolarisation but then when the Na channels become inactivated, they remain inactivated. The cell cannot repolarise and the Na channels remain in the inactivated state - and it mains a state of depolarisation.
Not broken down by AchE therefore it persists for longer.

Question 6

Give basic details about myasthenia Gravis

Answer 6

Autoimmune destruction of the nAchR.
Decreased end plate potentials as there are less receptors for the ACh to bind to.
Patient feels fatigued and weakened.
Can give AchE inhibitors that will inhibit the enzyme that breaks down ACh so that it persists in the NMJ for longer.

Question 7

Name some processes that calcium drives.

Answer 7

Necrosis
Release of neurotransmitter
Fertilisation
Imperative for bones and teeth 
Apoptosis

Question 8

What are the relative concentrations of calcium inside and outside the cell?

Answer 8

Outside
1-2mM

Outside
100nm

10,000 fold decrease inside.

Question 9

How is the calcium gradient set up and then maintained ?

Answer 9

1. The calcium channels are either open or closed.
2. Dependent on the cells ability to expel ca2+.
   - Ca2+ ATPase - uniporter - expels the calcium out - high affinity low capacity.
   - NCX- responsible for most expulsion. 3Na in and 1 Ca2+ out. High capacity but low affinity.
   - calcium buffers such as calmodoulin and synaptotagmin.

Question 10

Describe the 3 processes by which intracellular calcium is elevated.

Answer 10

1. Membrane permeability
   - opening of the VOCC.
2. Release from rapidly releasable stores
   - IP3 released from activation of Gq. This binds to its receptors on the SER which then releases calcium from the SER.
   - CICR - calcium released from the SERCA binds to ryanodine receptors on the SERCA which releases even more calcium. This cycle amplifies the amount of calcium released.
3. Release from non-rapidly releasable stores.
   - the mitochondria mops up calcium when the conc of calcium is high, acting as a protective mechanism. Some can be released from here too.

Question 11

How are calcium levels returned back to normal?

Answer 11

• recycle calcium back into the SER.
• mitochondria use of calcium
• capacitative calcium entry

Question 12

What is capacitative calcium entry?

Answer 12

This is to do with bringing calcium levels back to normal.
The SER literally sends out a signal when it its calcium stores are depleted.
The signal is a ‘depleted’ signal.
The signal indicates that uptake of calcium is needed.

Question 13

Explain how action potentials open Ca2+ channels in cell membranes.

Answer 13

The depolarisation that arises due to the influx of sodium causes VOCC to open, and hence there is a massive influx of calcium, as there is a 10,000 fold higher conc of calcium outside than inside the cell.