P: Neuromuscular junction Flashcards
What is NMJ an example of?
A chemical synapse
- Nerve meets muscle (no direct contact)
Overview of events at the NMJ
- Acetylcholine is released into the synaptic cleft
- ACh binds to receptors on muscle
- Triggers EPP in muscle cell
- Sets up action potential in skeletal muscle
- Muscle contracts
2 other names for somatic motor neuron?
Alpha motor neuron and lower motor neuron
Where is ACh produced?
In the cytosol of the presynaptic nerve terminal
Where is ACh stored?
In pre-synaptic vesicles which are made in the cell body of the neuron
What must the vesicles do to release neurotransmitters into the synaptic cleft?
They must DOCK at the active zones of the presynaptic membrane, then they must be PRIMED to FUSE with the presynaptic membrane
Summary of SNARE protein function
- Action potential
- Syntaxin and SNAP-25 (t-SNARE proteins) form a complex.
- Synaptobrevin (one of the 2 v-SNARE proteins) joins with this complex and the 3 proteins pull the vesicle closer to the membrane
- Ca++ enters the presynaptic neuron and binds to synaptotagmin (the other v-SNARE protein), causing fusion of the vesicle and subsequent ACh release in the synaptic cleft (exocytosis)
- SNARE proteins are dissembled –> need ATP
- Vesicle is recycled
How does ACh release lead to a muscle AP?
- Binding of ACh to its nicotinic receptors allows flow of Na+ and K+ through the receptor (receptor = ligand gated ion channel)
- The movement of ions leads to generation of EPPs (more ACh = more EPPs)
- Enough EPPs create an AP
What is the relationship between the release of NT and the amplitude of the EPP?
The greater the release of NT, the more ACh, the greater the amplitude of EPP
What is ACh split into and by what?
It’s broken down by acetylcholinesterase (AChE) into acetyl CoA and choline
What is an mEPP?
Even in a resting neurone small amounts of ACh are released into the synaptic cleft. This causes tiny depolarisations in the resting muscle cell membrane which is a mEPP.
What is myasthenia gravis?
Decreased numbers of functioning ACh receptors
How is myasthenia gravis treated?
With the therapeutic use of anticholinesterases to block the breakdown of AChE and therefore enhance activity of ACh
Effect of botulinum toxin?
Reduces release of ACh neurotransmitter
Effect of curare toxin?
Curare binds onto the Acetylcholine receptors on the motor endplate and block their binding with Acetylcholine. This blocks the action of acetylcholine which impairs the mechanism of muscle cell depolarization and subsequent contraction
