4 - Green - Neuromuscular Junction Flashcards
(37 cards)
Where does the axon make contact with the muscular fiber?
Neuromuscular Junction (NMY) or end-plate
NMJ Neurotransmitter
Acetylcholine (ACh)
Postjunctional Fold
Invagination of muscle membrane at the NMJ
Acetylcholine Resecptor (AChR)
Neurotransmitter receptor present on muscle membrane at the NMJ
What enyme breaks down ACh in the synaptic cleft?
Acetylcholinesterase
Active Zones
Regions of presynaptic membrane where synaptic vesicles fuse and release ACh
Oriented directly over post synaptic clefts
Highest density of AChRs at crests of post junctional folds
What occurs once motor neurons release ACh?
ACh binds to AChR’s on the muscle membrane
Activates Voltage-Gated Na+ Channels
Na+ enters cell, K+ exits = Depolarize (move towards ENa)
Action Potential! Muscle Contracts!
Acetylcholine broken dowon by ACh’Esterase
How can current generation at the NMJ be measured?
Electromyography (EMG)
What does the fusion of synaptic vessicles require?
Ca2+ dependent channels drive fusion
Once sodium (Na+) enteres the channel what is the current generated called?
End-Plate Current (EPC)
What is the result of EPC on voltage?
What is this change in potential called?
Becomes more positive (depolarize)
End-Plate Potential (EPP)
When when not stimulated, what are changes in muscle membrane potential called?
What causes this?
Miniature End Plate Potentials (MEPPs)
Look like EPPs, but much smaller
Caused by spontaneous release of quanta of ACh
Safety Factor
Why is this important?
Difference between actual EPP and threshold potential required to generate action potential
“Buffer Region”
ACh stores are not unlimited, this region ensures repetitive stimulat can still generat action potentials
What else can bind to AChRs (their other name…)
What is their general structure?
Nicotine
Nicotinic AChRs
5-subunit protein, creating a central pore
Are adult and embryonic nicotinic AChR’s the same?
No, embryonic has delta subunit, adult has epsilon subunit
Embryonic: Longer Open, Lower Current
Adult: Shorter Open, Greater Current
How does the NMJ form?
AChRs pre-aggregate in center of developing muscle fibers
AChRs become concentrate at region of interaction; increased by nerve
Existing receptors redistributed, new receptors made
Immature post-synaptic junctions present in developing muscle
What proteins drives receptor clustering?
What releases it?
Agrin, released from the nerve
“Aggrin’gate”
What protein does agrin activate?
What is its role?
Agrin activates Muscle-Specific Kinase (MuSK)
MuSK induces clustering by Rapsyn
“Rapsyn (wrapping) up the clusters for gifts”
The ‘K’ in MuSK is a kinase–it targets something for activation, it’s a middle-man
What additional protein is required for Agrin to bind to MuSK?
What regulates this binding?
LRP4
Agrin regulates
What additional protein is required for MuSK activation by the Agrin+LRP4 complex?
Dok-7
What is the terrible mneumonic for the clustering of AChR’s?
Now, you’re ALMost DR CAstillo
Nerve
Agrin + LRP-4
MuSK + Dok-7
Rapsyn
Cluster AChRs
What prevents clustering of receptors where they’re not needed? (e.g. negative signals)
ACh activates negative pathways
When do the embryonic receptors disappear (in favor of adult)?
After innervation during development
How many neurons are required per muscle fiber?
1 fiber = 1 nerve
