Neuromuscular Junction Flashcards
What is a motor unit?
One motor neuron innervates one group of muscle fibers
What happens to cause an action potential in the muscle fiber?
Motor neuron releases ACh
AChRs allow influx of Na and efflux of K
Leads to activation of v-g Na channels and action potential propagation
What is the end-plate current?
Entrance of Sodium ions into the muscle fiber
What is the end-plate potential?
The change in muscle fiber potential, more than enough to produce a postsynaptic action potential
What are miniature end plate potentials?
Like EPPs, but much smaller in amplitude
Caused by spontaneous release of quanta of ACh
What is the safety factor?
Difference between the actual EPP and threshold potential required to generate muscle action potential
EPP is more positive than threshold
What is the structure of a nicotinic AChR?
5 subunits arranged around a central pore
2 a, 1 B, y, and delta
What is characteristic of an embryonic AChR?
Longer single channel mean open time and lower single channel current
What is characteristic of an adult AChR?
Shorter single channel mean open time and greater single channel current
How does the motor neuron know where to form synapses?
Motor neuron releases ACh before making contact
Muscle membrane responds to ACh before contact
Synapses form where these interactions take place
Where are AChRs located before innervation?
Aggregate in center of developing muscle fibers
How does the nerve induce increased clustering of receptors?
Preexisting receptors are redistributed
New receptors are synthesized
Turnover is decreased
What is the function of agrin?
Released by the nerve
Initiates AChR clustering by regulating the interaction of MuSK and LRP4
What is the function of Dok-7?
Required to activate MuSK after binding of agrin and thus aggregate AChRs
What is the function of rapsyn?
Binds to AChRs and aggregates them to synapses
Other components of NMJ co-cluster with AChRs
What occurs after innervation?
Receptor half-life increases, embryonic receptors disappear and adult receptors appear
How are excess innervations by other motor neurons eliminated in the developing NMJs?
In neuron that will be eliminated, number of receptors on muscle is reduced –> decrease in synaptic strength causes further loss of receptors –> cycle eventually leads to terminal withdrawal
What is the function of botulinum toxin?
Blocks ACh release
What is the function of curare and bungarotoxin (snake venom)?
Inhibits AChRs
What is the function of physostigmine and neostigmine?
Inhibits AChE
What is the function of tetrodotoxin?
Blocks Muscle Na channels
What is the function of Conotoxins?
Block neuronal Ca channels, muscle Na channels, and AChRs
Describe Myasthenia gravis
Most patients have antibodies against AChRs, some to MuSK
Causes reduced AChRs at NMJ
EPPs and MEPPs are smaller than normal
What are the clinical features of Myasthenia gravis?
Weakness and fatigue of voluntary muscles
Worsens on exertion
Ocular muscle weakness
What are the treatments for MG?
AChE inhibitors
Drugs to reduce immune response
Removal of AChR antibodies
Describe Lambert-Eaton syndrome.
Antibodies against presynaptic Ca channels
Affects primarily limb muscles
Exercise improves weakness
What are the congenital myasthenic syndromes?
AChRs
Dok7
MuSK
rapsyn
LRP4
Describe botulism
Caused by Clostridium botulinum
Affects autonomic nervous system as well as NMJ
Death can occur from respiratory muscle paralysis
What is botulinum toxin used to treat?
Muscle contractures and spasms, strabismus (cross-eyes) and headaches
How does ageing affect the NMJ?
NMJ becomes unstable over time
Synaptic area decreases as AChRs fragment and number of postsynaptic folds decreases
Eventually lose motor nerves
Reinnervation is less likely to occur
