5.1 Electrical Excitability Flashcards
What causes the release of neurotransmitter?
The significant rise in the intracellular Ca2+ concentration
In nerve terminals, what kind of channels are present?
Voltage-gated Na+, K+ and Ca2+ channels
Describe the structure of a Ca2+ channel
6 transmembrane domains
4 units
What can block L type Ca2+ channels?
DHPs (dihydropyridines)
Eg. Nifedipine
Describe the process of transmitter release into the synaptic cleft.
Ca2+ enters through Ca2+ channels. It then binds to synaptotagmin. This brings the vesicles close to the pre-synaptic membrane. A snare complex forms between the membrane and the vesicle to make a fusion pore. The transmitter is then released through this pore and diffuses out into the synaptic cleft.
How does acetylcholine release cause a response in the next axon?
ACh activates nicotinic ACh receptor channels. ACh acts as a ligand. When ACh binds to the receptor, the protein goes through a conformational change and the pore opens. The pore allows Na+ and K+ to move through. More Na+ moves IN than K+ OUT so the membrane depolarises.
How is acetylcholine removed from the synaptic cleft?
It is reabsorbed by the pre-synaptic cleft.
It is quickly degraded by acetylcholine esterase.
Explain how competitive blockers of nAChR work and give an example. What are the consequences? Can the effects be overcome?
Eg. Tubocurarine
The blocker binds to the ACh binding site so ACh cannot bind to cause a response. It results in less depolarisation. The effects can be overcome by increasing the concentration of ACh so it is more likely to bind with the receptor.
Explain how depolarising blockers inhibit nAChR and give an example. What are the consequences of this? Can the effects be overcome?
Eg. Succinylcholine
They activate receptors but are not broken down by ACh esterase. The Na+ channels open and become activated. When they are inactivated they will remain that way due to maintained depolarisation. No further depolarisation will occur.
Explain a ‘miniature end-plate potential’
Occurs when a synaptic vesicle randomly fuses with the synaptic membrane causing a release of acetylcholine even when unstimulated.
Why do people suffer from Myasthenia Gravis?
It is an autoimmune disease targeting nACh receptors. This causes complement mediated lysis and receptor degradation by antibodies. It results in muscle weakness and fatigue.
Why do muscarinic ACh receptors produce a slower response than nicotinic ACh receptors?
mAChr are coupled to G-proteins. G-proteins then trigger a response in the cell via a cascade mechanism.
