The NMJ Flashcards
What is a neuromuscular junction?
A synapse between a motor neurone and a skeletal muscle fibre
What signal does a NMJ propagate?
Action potential to muscle contraction
How far do presynaptic motor axons terminate from the sarcolemma of a muscle fiber?
30nm
How is the motor end plate modified to work as an NMJ?
Invaginations called post-junctional folds, which increase its surface area
What lines the sarcolemma of the post synaptic membrane end plate?
Nicotinic acetylcholine receptors (nAChRs)
What is the term used to describe the area where vesicles are grouped at the motor nerve terminal membrane?
Active zone
How many vesicles are roughly clustered at the active zone?
~50
What do vesicles in the motor nerve terminal contain?
ACh
How are vesicles in the active zone kept close to the membrane?
Docked by proteins dystrophin and rapsyn.
Where are the reserve pool of vesicles docked?
At the cytoskeleton further from the membrane
What docks the reserve pool of vesicles?
Actin microfilaments
What does the arrival of the action potential cause at the motor presynaptic terminal?
Opens voltage-dependent calcium channels and Ca2+ ions flow from the extracellular fluid into the presynaptic neuron’s cytosol.
What is the effect of calcium influx into the presynaptic terminal?
Causes several hundred neurotransmitter-containing vesicles to fuse with the presynaptic neuron’s cell membrane through SNARE proteins to release their acetylcholine quanta by exocytosis.
How do SNARE proteins lead to exocytosis?
The v-SNARES are associated with the vesicle membrane and the t-SNARES with the cell membrane these combine to form a cis-SNARE complex, also known as a “SNAREpin”.
What is the term used to describe acetylcholine release in packets?
Quanta
What does acetylcholine do after exocytosis?
ACh moves across synaptic cleft
The acetylcholine activates acetylcholine receptors, opening their ion channels which permits sodium ions to move into the endplate producing a depolarization
Roughly how many nAChRs are bound to from one quanta?
~2000
What is the depolarising effect of a single stimulation (single quanta)?
Depolarization of ~0.5 mV known as a miniature endplate potential (MEPP).
What is the time interval between the arrival of the nerve impulse in the motor nerve terminals and the first response of the endplate?
0.5 -0.8 msec
How many quanta are required to make an EPP?
~200
How do quanta need to be released in order to produce an EPP?
Released simultaneously or in rapid series by a nerve impulse
What is the EPP?
Chemically induced change in electric potential of the motor end plate.
Does an EPP always produce an action potential propagation?
No
How does an EPP lead to action potential propagation?
If the EPP depolarizes the cell to a crucial threshold level, it will fully activate sodium channels along the membrane and produce the action potential.
What enzyme hydrolyses ACh bound to receptors?
Acetylcholinesterase
How long does AChE take to act?
~0.16 ms
Where is AChE bound?
Post synaptic membrane
What happens to the liberated choline after breakdown?
Taken up again by the pre-synaptic neuron
What does AChE break ACh into?
Choline and Acetic acid
What happens to reabsorbed choline ?
ACh is synthesized by combining with acetyl-CoA through the action of choline acetyltransferase.
What antagonises nAChr?
Tubocurarine, Veruconium
What does tubocurarine do?
Antagonist of nicotinic ACh receptor
What does veruconium do?
Antagonist of nicotinic ACh receptor
When is veruconium used clinically?
Muscle-relaxing properties, which are used adjunctively to general anesthesia.
What drug can reverse the effects of nAChr antagonists and why?
Neostigmine which inhibits AChE therefore more ACh is in the cleft and can compete for the receptors.
What does suxamethonium do?
Depolarising drug, generates an action potential, AChE cannot remove the drug so the membrane cannot repolarise. The maintained depolarisation means that the voltage gated sodium channels are inactivatedm another AP cannot be propagated
Why do your muscles relax when you take suxamethonium?
Muscle relaxation separate process to nerve stimulation
What does botulinum toxin do?
Cleaves SNARE proteins meaning that the acetylcholine vesicles can’t bind to the intracellular cell membrane, preventing the cell from releasing vesicles of neurotransmitter.
What are the effects of botulinum toxin and what is it clinically used for?
Stops nerve signaling, leading to paralysis of muscles.
Used to prevent excessive sweating, fine lines on skin
What does neostigmine do?
Enhance cholinergic transmission by inhibiting AChE.
When is neostigmine clinically useful?
Used to improve muscle tone in people with myasthenia gravis (autoimmune disorder against nAChr).
On arrival of a single action potential, motor nerves release a number of quanta of transmitter approximately equal to..
100
