Signalling 2 Flashcards
How does GPCR work?
Ligand binding to receptor –> conformational change in cytoplasmic domain allows G-protein to bind/ be activated by receptor.
Activated G protein activates intracellular enzymes.
What type of G proteins do GPCR’s use?
GPCR’s use large, heterotrimeric G proteins, not small monomeric G proteins.
What are the effects of GPCR activation?
There is lots of different targets of activated alpha and beta gamma subunits.
Targets will be activated or inhibited directly or indirectly.
It commonly causes the production of a 2nd messenger.
How are G-proteins activated?
GTP is a similar molecule to ATP.
GTP bound G-proteins = active
GDP bound G-proteins = inactive
Activated G protein activates downstream effector proteins.
What are the off switch molecules for G protein activation?
GAP/RGS proteins
What is adrenaline, where is it produced and why?
-Adrenaline is a hormone produced by adrenal medulla after sympathetic NS stimulation in acute stress situations to increase heart rate etc.
Using the example of adrenaline, explain GPCR activation?
- Adrenaline binds to GPCR, triggers activation of G-protein alpha subunit, this activates enzyme adrenyl cyclase to produce 2nd messenger cAMP.
- cAMP activates PKA which does 2 things:
1. Phosphorylates and activates phosphorylase kinase. This phosphorylates and activates the enzyme glycogen phosphorylase, which catalyses breakdown of storage molecule glycogen, to produce glucose.
2. PKA phosphorylates and inhibits enzyme glycogen synthase, therefore glycogen synthesis does not occur.
Why is the adrenaline GPCR sequence like an on, off switch with no intermediate phase?
It wouldnt make sense as an intermediate phase would mean synthesis and degradation at the same time.
How can the signal in the adrenaline GPCR sequence be switched off?
G-protein alpha subunit hydrolyses the GTP, restoring it to inactive GDP. It can no longer activate adenyl cyclase, so no new cAMP is produced.
How are 2nd messengers broken down?
- Specific enzymes break down several 2nd messengers eg. phosphodiesterases remove cAMP
- Alternatively, Ca+ ions acting as 2nd messengers can be actively removed by using ion channel pumps, to pump them back into intracellular stores, or out the cell.
How is specificity of cell signalling acheived?
Some genomes of cells in different locations for response however, there is diffrent expressions of GPCR’s, G proteins, effector molecules and 2nd messengers produced. There fore leading to different specific response in each tissue.
This means that the same hormone can have different effects in different tissues.
How does electrical signalling work?
Electrical nerve impulses travel along the axon of a nerve cell.
Axons can be very long but nerve impulses travel very fast.
What is a nerve impusle?
A wave of altered charge across the nerve cell membrane that sweeps along the axon.
aka. an action potential, depolarisation
What is the ion conc. like in a resting cell?
At rest, there is a difference in ion conc. between inside and outside of cell. This is maintained by ion pumps in the plasma membrane.
Approx -70mV potential at rest, when the nerve cell is stimulated, action potential is generated.
How is an action potential generated?
1.Some stimuli can directly stimulate a nerve cell eg.olfactory (small) neurons
2.A neurotransmitter from a nearby neuron can bind to a receptor on the nerve cell. In this case, receptor activation causes ion movement that triggers AP in 1st neuron.
Either way threshold of -50 to -55mV needed.
What is the process of an action potential?
Na+ ion channels open; +charged Na+ ions flow into the cell and this increases membrane potential to around +40mV (depolarisation).
K+ ion channels open in response to depolarisation and Na+ channels close. K+ ions are pumped out (repolarisation).
K+ channels eventually close but usually overshoot (hyperpolarisation) at around -90mV. Slowly the Na/K pump restores the voltage to -70mV.
This AP moves along the axon.
When AP reaches end of neuron it must cross a synapse to set AP up in next neuron.
What is a refractory period?
Time immmediately following AP when new AP cannot be initiated in same area of membrane.
Meaning AP’s have one way travel.
There is an absoloute (when Na+ channels open) and relative (after that) refractory periods both exist.
What happens when there are multiple inputs to a nerve cell?
Some may be excitatory (ESP’s), some may be inhibitory (ISP’s).
They are added together at axon hillock by summation.
What are the 2 types of summation and the difference?
- Spacial; summation of inputs from different areas, such as from dendrites.
- Temporal; where same input occurs multiple times within a short time period. When this occurs with ESP’s, the threshold value for an AP can be reached quicker.
How is signal intensity communicated by an AP?
AP is always same magnitude, therefore info about signal intensity is transmitted not by magnitude but by frequency of AP generation.
More frequent AP’s result from a stronger signal and vice versa.
What is the importance of chemical signalling in the NS?
It is vital as most neurons dont act alone, they act with other nerve cells and communicate via a synapse.
Neurons use biochemical signals to cross the synaptic cleft: neurotransmitters.
What are synapses formed from?
From a presynaptic nerve cell axon terminus and a post synaptic nerve cell dendrite, with the synaptic cleft between.
What do neurotransmitters do and when are they released?
- Transmit signals across synapse.
- Release when AP reaches pre-synaptic neuron termini.
What is the action of neurotransmitters like?
Bind to receptors on dendrites of post-synaptic neuron.
They can be excitatory or inhibitory; will promote or inhibit formation of AP in receiving neuron.
Different neurotransmitters are associated with different nervous system functions and different locatiions in NS.
Many drugs act on neurotransmitter signalling.
