Electrical Excitabilty (synapse Transmission) Flashcards
How do signals pass from nerve to muscle?
Through the neuromuscular junction (synapse between nerve and skeletal muscle)
What channel are only found at nerve terminal
Depolarisation opens voltage gated Ca2+ channels
More AP means they open slower and for longer
What happens at a nerve terminal?
AP reaches voltage-gated Ca2+ channel.
This opens them
Ca2+ is released into the nerve terminal
Increased intracellular Ca2+ conc
Causes release of neurotransmitter via exocytosis
How can we increase the amount of Ca2+ entering the nerve terminal?
Increase the number of AP”S
Therefore increases neurotransmitter release
What is the structure of CA2+ channel?
Very similar to voltage-gated Na+ channel
Very diverse set (many numbers of them_
Can be blocked by DHP drugs. They block Ca2+ entry to regulate blood pressure
What are the roles of all the subunits present in Na+ and Ca2+ channels?
One subunit forms the pore making it a functional channel
Other subunits fine-tune the properties and enable correct regulation of the pore. (Eg that may have a target receptor for mediated effects such as a phosphorylation site for adenine to increase contraction_).
What are some things that are different about Ca2+ channes compared to Na+ channels?
Voltage-gated Ca2+ open more slowly than voltage-gated Na+
Ca2+ activate/inactivate more slowly than Na+
Ca2+ channel inactivation is Ca2+ dependent
What stops the muscle contraction after it receives an AP?
Acetylcholine esterase breaks down Ach stopping it binding form the muscle and so contraction stops.
How are neurotransmitters released?
Ca2+ entry through Ca2+ channel Ca2+ binds to synaptotagmin Vehicle bought closer to membrane Snare complex makes a fusion pore Transmitter releases through pore
How is the skeletal muscle depolarised?
The nictoinic acetylcholine receptor (nAChR) is a ligand gated ion channel (2 x Ach bind).
It’s permeable to cations (K+ and Na+), as the cells membrane potential is further from E(Na+) there is a large drive for Na+ to move in and so the cell becomes depolarised.
What are the two types of nicotinic ACh blocker?
Competitive blockers - block channel
Depolarising blocker- close and desensitise channel so become inactivated
Give an example of a competitive block for nicotinic ACh receptor and how to overcome it.
D-tubocurarine is a competitive blocker
It can be overcome by increasing the concentration of ACh
Give an example of a depolarising blocker of NACh receptor and how it works.
Succinylcholine is a depolarising blocker.
It binds to NAChR (muscle may twitch) but then cannot be degraded by ACH esterase so remains bound permanently.
This causes the membrane to maintain depolarisation so the adjacent Na+ channels wont be activated as they are stuck in the inactive state as nor refractory period has occurred
What are neuromuscular blockers used for?
In surgery they cause paralysis to my it easier.
Must be used carefully with anaesthetic or th patient will be in severe pain but too paralysed to say so.
Suggest a disease of the neuromuscular junction an explain its causes etc.
Mayasthenia gravis- (autoimmune disease targeting nACh receptors)
Caused by antibodies directed against nAChR on the postsynaptic membrne of skeletal muscle
Antibodies lead to loss of functional nAChR by complement mediated lysis and receptor degradation
End plate potential have reduced amplitude
