Week 4 MPW Lecture 11 Flashcards
Why is signalling vital and what are the uses of signalling?
Signalling is vital for response to hormones, growth factors, infection etc; neural synapses; bacterial response to environment.
How can signals enter the cell?
Include:
a) Ion channels
b) G protein coupled receptor
c) Kinases (Enzymes)
d) Normal diffusion
How can ion channels used to signal?
These are ligand-gated channels and need to be very responsive to ligand concentration.
a) a sharp transition needs allostery i.e. multiple subunits
b) Therefore, ion channels have multiple subunits (often 5), to make them respond more dramatically to change in ligand concentration
What are the pros and cons of using an ion channel as a transmembrane receptor?
Pros:
a) advantage that they can turn on a signal very rapidly – roughly 1 ms.
b) Cons:
c) reversing the signal requires removal of all the ions, which can use a lot of energy.
i) Speed is sometimes critical (vision; muscles; nerves) so ion channels are used here.
Ion channels are not very specific, so more specific signals (growth, differentiation) tend to be one of the others
An example of an ion channel?
Acetyl choline receptor (a ligand-gated sodium/potassium channel) – typically on the postsynaptic membrane
a) Interesting that there are 5 possible binding sites, but it only binds at two of them.
So it is not as cooperative as it could be – but requires only two ligand molecules
How do ion channels work?
Ion channels are opened by ligand binding. Typically it takes more then one ligand binding to open the channel, which makes it more cooperative (sharper response). The ion channel opens by rotating helices, like opening the lens of a camera
Give two examples of signals that have to be transmitted very fast
Vision, pain and nerve signals
Give two examples of signals that take a long time (days or more) to show an effect
cell differentiation and sexual development (puberty)
Describe the four main types of signal. For each, give an example of a signal that works in this way (you will need to look these up!)
(a) Crossing the membrane directly: Steroid hormones (eg testosterone or oestradiol) or retinoic acid.
a) (b) Ion channel: nicotinic acetyl choline signalling on the postsynaptic membrane
b) (c) G-protein coupled receptor. Lots of examples in lecture 13 eg rhodopsin (vision)
c) (d) Receptor–linked kinase, for example vascular endothelial growth factor (VEGF) which stimulates the growth of new blood vessels.
What is the advantage for an ion channel of requiring more than one ligand molecule to bind in order to turn on the signal? (Try to write this down in a coherent explanation)
An ion channel that is turned on by a single ligand will have a hyperbolic curve of activity vs ligand concentration. The problem with this is that even small amount of ligand will activate a signal, and the effects just weakens as the ligand concentration increases. A channel turned on by binding of several ligands will have a much steeper curve, like a sigmoid curve. This is much more like what you want – little activation at low ligand concentration, followed by a sensitive response to small increase in ligand concentration.
Describe how the acetylcholine receptor works to transmit signals across a synapse
When an action potential reaches the end of an axon, it stimulates the opening of a calcium channel, which leads to the fusion of synaptic vesicles with the presynaptic membrane. This releases acetylcholine into the synapse, which diffuses rapidly across the short distance to the postsynaptic membrane, and binds to nicotinic acetylcholine receptors there. This leads to opening of the receptors, which are sodium/potassium channels. This sets off an action potential.
There are two completely different types of acetylcholine receptor (nicotinic and muscarinic). Look them up. Which one is this, and what does the other one do?
As above, this one is nicotinic (which means it is opened by nicotine – this is why cigarettes have the effect they do). Muscarine is a poison extracted from mushrooms.
