View source for 4. The neuromuscular junction

=== Learning objectives ===

* What is the neuromuscular junction?
* Where does the presynaptic nerve fibre originate, and what type of neuron is it?
* What is the neurotransmitter of the neuromuscular junction?
* What is the postsynaptic receptor of the neuromuscular junction?
* What is the motor end plate? Describe its structure
* What is the end plate potential, and what is the magnitude of it?
* Describe the steps of synaptic transmission at the neuromuscular junction
* What is curare, and how does it work?
* What are the differences between the neuromuscular junction and CNS synapses?

=== Neuromuscular junction ===
The neuromuscular junction (NMJ) is the most important synapse. It’s the synapse between the nervous system and the skeletal muscle. More specifically, it’s the synapse between the axon of the alpha motor neuron in the anterior horn of the spinal cord and the skeletal muscle it innervates.

Like all chemical synapses, there is a neurotransmitter and a postsynaptic receptor which recognizes the neurotransmitter. The postsynaptic membrane of the neuromuscular junction is called the ''motor end plate'', a term which is also sometimes used erroneously to describe the neuromuscular junction as a whole. The motor end plate is part of the cell membrane of the muscle fibre, called the ''sarcolemma''. The motor end plate has many invaginations which increases its surface area, making more space for postsynaptic receptors. There are approximately 10 000 receptors per square micrometer.

The neuromuscular junction is a relatively simple chemical synapse and is therefore often used as a model for chemical synaptic transmission.

==== Acetylcholine and nicotinic acetylcholine receptors ====
The neurotransmitter of the neuromuscular junction is ''acetylcholine''. The postsynaptic receptor of the NMJ is the ''nicotinic'' acetylcholine receptor (not the muscarinic type).

The presynaptic neuron produces acetylcholine and stores them in small vesicles. These ''presynaptic vesicles'' are stored close to the presynaptic membrane, where they wait until the presynaptic membrane gets depolarized.

==== EPSP of the neuromuscular junction ====
The postsynaptic potential of the neuromuscular junction is always excitatory (EPSP) and is called the ''end plate potential'' (EPP). The EPP is much larger than the average EPSP, normally having an amplitude of 50 mV. Only about 30 mV is needed to reach threshold, so this is more than enough for a single EPP to cause depolarization of the motor end plate.

Because the EPP is much larger than needed to reach threshold, there is a so-called ''safety factor'' of approx. 20 mV. This means that if the EPP were to be reduced for any reason it would still be enough to reach threshold, as long as it wasn’t reduced more than the safety factor. Reduction of EPP is one mechanism of muscle fatigue, which we’ll discuss in topic 8.

==== Steps at the neuromuscular junction ====
An action potential travels down the axon of the alpha motor neuron, eventually reaching the presynaptic membrane, which becomes depolarized. This depolarization opens voltage-gated Ca2+ channels on the presynaptic membrane, which allows Ca2+ to flow into the end of the axon. This Ca2+ inflow triggers the release of acetylcholine from the presynaptic vesicles into the synaptic cleft.

The acetylcholine diffuses across the synaptic cleft and binds to the nicotinic acetylcholine receptors on the motor end plate. The nicotinic acetylcholine receptor is a non-selective cation channel, meaning that when acetylcholine binds to it, the ion channel will open and allow Na+ and K+ to enter the cell.

The influx of positive ions into the motor end plate causes an ''end plate potential'' (EPP) to form, which causes the threshold to be reached. This causes voltage-gated Na+ channel to open, which causes depolarization. This will initiate a series of events which eventually cause the muscle to contract.

After having bound to the nicotinic acetylcholine receptors and having caused the EPP, acetylcholine will eventually unbind from the receptor. The enzyme ''acetylcholinesterase'', which exists in the synaptic cleft, will ''hydrolyse'' (break down) acetylcholine into acetate and choline. This “ends” the synaptic transmission. Choline is taken up by the presynaptic membrane which will reuse it to form more acetylcholine, getting ready for the next action potential to arrive.

==== Curare ====
Curare is a type of plant poison which indigenous people of America used to poison arrows. This poison paralyses the target, making it very useful for hunting. The most important type of curare is ''tubocurarine''.

Curare works by preventing acetylcholine from binding to the nicotinic acetylcholine receptors, thereby preventing motor neurons from stimulating skeletal muscle. The poison occupies the same position on the receptor as acetylcholine itself does, but it does not stimulate the receptor. Because the receptors have already been occupied by curare, acetylcholine can’t bind to them.

Curare is mentioned a lot in physiology, and several drugs used as skeletal muscle relaxants are derivatives of it, so it is useful to know how it works.

==== Differences between NMJ and other synapses ====
While the events at the neuromuscular junction are generally similar to those of other synapses, there are some ways in which the NMJ is atypical compared to other synapses.
{| class="wikitable"
|'''Neuromuscular junction'''
|'''Other synapses (mainly in the CNS)'''
|-
|Each muscle fibre is innervated by only one motor neuron
|Each neuron is innervated by hundreds or thousands of neurons
|-
|Each motor neuron innervates only one muscle fibre
|Each neuron is innervated by hundreds or thousands of neurons
|-
|The postsynaptic potential (the EPP) is large enough to cause depolarization alone
|Most EPSPs are subthreshold, meaning that more than one is required to cause depolarization
|-
|The NMJ is only excitatory
|The CNS contains both excitatory and inhibitory synapses
|-
|There postsynaptic membrane has only one type of receptor
|The postsynaptic membrane normally contains more than one type of receptor
|}
[[Category:Physiology 1]]