Neuromuscular junctions Flashcards
What is the neuromuscular junction?
A specialised synapse between a motor neuron and a muscle cell.
The cell body is found in ventral horn of the spinal cord.
What are the features of NMJ that differentiate from other synapses?
The postsynaptic membrane shows invaginations/folds, this increases the surface area of the membrane.
This allows high level of expression of post synaptic receptors.
There is also a high density of vesicles containing neurotransmitters.
What is the appearance of NMJ under a microscope?
Shows the folds in the postsynaptic membrane.
Dark density because there are many proteins and receptors.
What is the role of Ca2+ in NMJ?
Ca2+ enters the cell through VGCaC, which open in response to depolarisation from an action potential.
Ca2+ triggers exocytosis:
The vesicle containing the neurotransmitter Acetylcholine docks with the membrane.
It opens up and allows the diffusion of ACh into the synapse.
What is synaptotagmin?
A Ca2+ sensor.
Ca2+ binds to synaptotagmin and this causes a change in conformation which triggers vesicle fusion with the membrane.
What is the ACh receptor?
The nicotininc ACh receptor (nAChr), on the postsynaptic end-plate membrane.
ACh binds, causes a conformational change which opens up a pore in the protein, which ions can move through.
What is the structure of nAChR?
Transmembrane spanning protein
5 subunits - 3 Beta2s, 2 Alpha 4s,
With 2 binding sites - 2 ACh need to be bound for a conformational change to occur.
How are NMJ synapses specialised?
Multiple quanta - 100s of vesicles - are released.
The postsynaptic membrane is folded so there is a high density of nACh receptors that ACh binds to, and a high density of VGNaC.
What is End Plate Potential?
Lots of Na+ enters the cell, so there is lots of depolarisation.
From RMP -90mV in NMJ, to -20mV.
see picture
What is the process of end-plate potential?
ACh binds to nACh receptors.
Channel opens, permeable to Na+ and K+.
The Em of the muscle cell is -90mV.
There is a greater influx of Na+ than K+.
The end plate potential is -20mV.
Why is there a large influx of Na+ during EPP?
There is a high chemical and electrical driving force for Na+ through ligand gated channels - because there is a low [Na+] inside the cell, and the Em is -90mV, so attracts positive Na+.
Depolarisation causes VGNaC to open, so there is a larger influx, and generates an action potential.
Why is there less influx of K+ than Na+?
There is little electrical driving force because the RMP is negative, and K+ is positive.
Chemical force drives it out, because of high [K+] in cell, but
Equilibrium potential for K+ is -90mV, so at RMP, K+ is at rest.
Then, depolarisation occurs, Em rises to -20mV, further from the equilibrium potential of K+, so K+ leaves the cell.
How does an action potential travel to the muscle?
EPP decays as it moves away from the end plate, as nAChRs are absent away from synapse.
The EPP triggers an action potential, which is able to propagate across the membrane of the muscle cell because of Voltage Gated channels, and into the muscle cell.
What is the speed of EPP?
Presynaptic action potential to EPP is 1millisecond.
This is because ACh is quickly taken out of the synapse.
How does the action potential enter the muscle?
Action potential travels through Transverse-tubule system, where it invades the muscle along the membrane.
This allows transmission of the action potential deep into the muscle fibre to separate myofibrils.
How is Ca2+ released from the SR?
Depolarisation triggers DHP receptor / L-type Ca2+ voltage-gated channel.
Tethers this protein to another protein on sarcoplasmic reticulum.
Ca2+ is stored in the SR, so can come out when pore is open by depolarisation.
How does Ca2+ reenter the SR?
Repolarisation - the action potential goes away.
The plug goes back into Ca2+ release channel in the SR.
Ca2+ is pumped back in and binds to calsequestrin.
How does motorneuron activity lead to muscle contraction?
Action potential causes a twitch in the muscle.
For contraction, more synaptic events need to occur quickly - summation.
40 action potentials are needed for sustained contraction.
How is ACh removed?
ACh is hydrolysed by acetylcholinesterase into choline.
Choline is taken back up to be resynthesised into ACh.
What does a failure of an NMJ cause?
Inability to contract muscles.
Most used skeletal muscle is the eyes - inability causes Myesthenia Gravis.
Reduced number of nAChR on the postsynaptic membrane.
Treatment involves AChE inhibitors, which blocks acetylcholinesterase, so allows prolonged signal.
