The Neuromuscular Junction Flashcards
what is a neuromuscular junction?
The junction between a motor neuron and a myocyte (muscle fibre)
There are many neuromuscular junctions along the length of a muscle to ensure that all the muscle fibres contract simultaneously ensuring a powerful muscle movement.
what does a NMJ allow for?
It allows for rapid and reliable neurotransmission
The strength of synaptic transmission at each NMJ virtually guarantees that all muscle fibres contract rapidly in response to every single action potential conducted.
what is the role of Ca2+ in excitation- contraction coupling?
Action Potential in presynaptic terminal
Depolarisation opens voltage gated Ca2+ channels
Ca2+ influx into presynaptic terminal (down concentration gradient)
Ca2+ entry into presynaptic terminal triggers vesicle fusion
Ca2+ sensor is a synaptotagmin – it changes its conformation on Ca2+ binding to it which triggers vesicle fusion
Neurotransmitter released (e.g. Ach) by exocytosis
what receptor is at the post synaptic membrane of a NMJ and what is its structure?
Nicotinic Acetylcholine receptor
5 Subunits of proteins
Two binding sites for ACh: So two molecules of ACh bind to confirmational change
what happens at the nAChr when ACh binds to it?
ACh binds to nicotinic ACh receptors (ligand-gated ion channel) on postsynaptic membrane
Ligand gated ion channel: When ACh binds a conformational change occurs which opens the pore to allow ion movement
what happens at a generic synapse (NOT NMJ)?
An excitatory neurotransmitter is released and will bind to an excitatory ionotropic receptor - this could be an ACh nicotinic receptor
2 molecules of ACh binding to the receptor causing Na+ influx and membrane depolarisation
Small excitatory post synaptic potential (EPSP)
what components makes the pre- synaptic neurone of a NMJ a specialised synapse?
Lots of mitochondria
More vesicles containing neurotransmitter than any other synapse in the CNS
Multiple active zones for release of large amounts of neurotransmitter simultaneously
One action potential causes the release of 200-300 quanta, all releasing their 4000 molecules of ACh each (much more than a generic synapse)
what components makes the post- synaptic neurone of a NMJ a specialised synapse?
Junctional folds
Very high density of nACh receptors
high density of voltage gated Na+ channels
Motor end plate is equivalent of post synaptic neurone in a generic synapse.
what is an end plate potential?
the voltage produced solely by ACh binding to nAChR on motor end plate. They result in an action potential being generated
EPP is very large (compared to most synaptic potentials e.g. EPSP) – Many ACh vesicles released; high density of nAChRs
how is EPP different to AP?
EPP and an Action potential are two separate events. AP produce by opening of VG Na+ ion channels
Timing: Pre-synaptic AP to EPP generation in post-synaptic membrane ~ 1 msec
how is an AP generated at the NMJ?
The resting membrane potential at the motor end plate is -90mV compared to that of a neuron which is -65mV.
A lot of ACh released - ACh binds to nAChRs on postsynaptic end-plate membrane (2 ACh molecules required to activate receptor)
Thousands of nAChR receptors are activated - channel opens – permeable to both Na+ & K+
Na+ influx is much greater than K+ efflux
This results in a 70mV worth of depolarisation, and the end plate potential changes to -20mV (peak).
This massively exceeds the threshold value so VG Na+ ion channels are able to open (more Na+ influx) - generate an action potential.
This makes the synapse highly reliable i.e. will cause an action potential
what is the fate of ACh after its bonded to the nAChr?
ACh binds to nAChR for ~ 1 ms
Released back into synaptic cleft - hydrolysed by Acetylcholinesterase (AChE) into choline and acetate.
Choline can then be taken up by the presynaptic neuron and used to make more ACh.
as you move away from the motor end plate, what happens to EPP and AP?
EPP decays as you move further away from the motor end plate. Smaller EPPs are being generated as density of nAChRs decreases as you move from the synpase.
However VG Na+ ion channels are present all across the membrane of the muscle fibre
Therefore the size of action potentials remain constant as you move away from the motor end plate.
Red – EPP
Blue – action potential
after the NMJ, what happens to the post synaptic AP?
Action potential invades T (transverse) -tubule system.
The T- tubules allows the transmission of the AP to move away from the motor end plate and to separate myofibrils to cause contraction
Sarcoplasmic reticulum is where the calcium needed for contraction is provided from in response to depolarisation
what is a DHP receptor?
functions in skeletal muscle essentially as a voltage sensor, triggering intracellular calcium release
The DHP receptor is tethered to the ryanodine receptor (located Ca2+ release channel).