Neuromuscular Junction Lecture Flashcards
How are transmitters release ?
An action potential reaches the pre-synaptic neurone which causes voltage gated Ca2+ channels to open.
2) Ca2+ enters
3) Ca2+ binds to synaptagmin.
4) vesicles that contains ACH is brought close to membrane
5) fuses with membrane and transmitter is released through this poor
What type of receptors do ACH bind to in a neuromuscular junction ?
- nicotine’s ACH receptors which is a ligand gated ion channel.
- this ligand gated ion channels are permeable to cations such as k+ and Na+.
What is the structure of a voltage gated Ca2+ channel ?
- comprises of one alpha subunit With 4 domains ( similar to Na+ voltage gated channels)
- it contains S4 regions which have positively charged amino acids.
- Ca2+ activation is Ca2+ dependant.
What is the role of S4 regions in voltage gated Ca2+ channel ?
- they help to detect changes in membrane potential
- for example , when a membrane is becoming depolarised , they undergo a conformational change which causes the voltage gated Ca2+ to open , this causes Ca2+ to then enter the membrane.
What are the two types of blockers of nicotinic ACH receptors ?
1) competitive blocker
2) depolarising blocker
What are a few differences between Na+ voltage gated channels and calcium voltage gated channels ?
- calcium V activate more slowly than Na V.
- Ca2+ inactive more slowly than Na+ V channels.
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What is the function of competitive blockers eg d -tubocuraruine.
- they bind to ACH receptors
- they prevent conformational change of ligand gated Na channels
- this reduces synaptic transmission
- ACH cannot bind.
- this causes paralysis
What is an example of competitive blockers ?
- d-tubocurarine
What are the functions of depolarising blockers
- they bind to ACH receptors
- in the first round , they will cause a conformational change in the ligand gated channels . This would cause a very slow depolarisation. However , Na+ channels will then become inactivated , so a wave of depolarisation cannot occur and no action potentials generated
How do local anaesthetics work ?
- they block go,take gated sodium channels , which prevents depolarisation of cell membranes of nerves.
- neuromuscular blocking agents are added on top of this , this helps to paralyse muscles which makes the surgery easier.
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What is an example of a depolarising blocker ?
Succinylcholine
- succinylcholine binds to ACH receptors , causes depolarisation in the post-synaptic neurone. ACH esterase does not break down succinylcholine. This causes prolonged depolarisation - sodium channels become inactivated so cannot activate another action potential
What is the cause of mayasthenia gravis
- autoimmune disease
- antibodies bind to the nicotinic receptors on the muscle.
- this reduces synaptic transmission.
What are consequences of myesthenia gravis ?
- muscle weakness
- fatigue
- endplate potentials are reduced in amplitude
How can you diagnose myasthenia gravis ?
- Ask a patient to do repeated facial movements which would provoke muscle weakness.
in a hospital environment , you will administrate a short acting anticholinesterase which prevents the breakdown of ACH - this will allow ACH to last longer in the synaptic cleft making it easier to bind to receptors
- the facial weakness is relieved.
What are consequences of organophosphate poisoning ?
- organophosphates are eusually used in insecticides.
- they form a stable irreversible covalent bond to ACHesterase.
- ACH concentration increases.
