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Nerve Cells & Synapses
Written by Tim Sheppard MBBS BSc. Last updated 14/8/12

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What is a nerve cell?

For the benefit of simplicity, we're going to focus for now on the somatic nervous system - i.e. the nervous system which we have conscious control over. The mechanisms of communication are very similar throughout the nervous system, but there are slight differences which are better understood after an appreciation of the basics.

You probably know a nerve as the fibre which carries information from one part of the body to another - and you'd be absolutely right, this is what nerves do. However, nerves aren't simply long bits of metal like electrical wires. They have cell bodies, like most cells, containing organelles including a nucleus. They are also packed full of mitochondria because communicating requires so much energy.

The basic structure of a nerve cell involves the cell body - the 'star-shaped' structure in the middle - with a large array of pointy bits coming out: the axons and dendrites. In actual fact, the axons are the parts of the nerve cell which send information out to other cells, carrying the 'on' signal when required to the specific cell which requires it. The dendrites receive information, via synapses, and return this to the cell body to be dealt with in whatever manner is appropriate (often it is simply passed on to be delivered, via an axon, to the next cell).

The communication requires movements of ions in and out of the cell all the way along these axons and dendrites. In order to maintain the concentration gradients that make this movement possible, a large amount of energy is required, so mitochondria are found throughout these extensions of the cell - not just the cell body.

What is ACh?

In order to pass information from one cell to another, a neurotransmitter must be used. This must be a chemical which can activate receptors on the second cell, and incorporates a whole range of substances. One particular neurotransmitter is acetyl choline (or ACh for short), which is used in many of the synapses in the body.

ACh is made up of two very simple chemicals - acetic acid (or acetate) and choline, joined by an ester bond in the middle. It is a simple chemical, synthesised in the ends of nerve cells just before the synapse, so that it is in the right place for transmitting a signal.

How do nerves work?

The idea with nerves is that they carry information from one part of the body to another. To make this as simple as possible, each nerve is switched on and off very quickly by an action potential - it is effectively a binary signal. When an action potential passes along a nerve, the nerve is said to be stimulated, and at its opposite end it will stimulate the next nerve with an 'on' signal.

To get a more complicated signal back to the brain, or from the brain to the body, more nerves must be involved. For instance, to tell the brain that your right thumb feels pain and intense heat, nerves to communicate pain must be switched on, and nerves to communicate heat must do the same - and each of these carries their 'on' signal through to the brain.

In order to transfer the action potential from one nerve to the other, a neurotransmitter such as ACh must be passed across a synapse.

What is a synapse?

A synapse basically refers to the gap between one nerve and another nerve, but will be used for our benefit to include the gap between one nerve and a muscle fibre (which is given the special name, neuromuscular junction).

It comprises three parts:

a) The pre-synaptic membrame
b) The synaptic cleft
c) The post-synaptic membrane

The pre-synaptic membrane is the membrane of the part of the cell just before the synapse. This is the point of the first cell which passes on the 'on' signal to the next cell.

The synaptic cleft is simply the gap between the two cells, through which the neurotransmitter must pass in order to stimulate the next cell.

The post-synaptic membrane is the part of the next cell which is stimulated by the neurotransmitter - which receives the signal from the first cell, and which then effects a response.

In our particular synapse of interest, we're looking at ACh as the neurotransmitter. The post-synaptic membrane therefore needs an acetylcholine receptor, the NAChR, and an enzyme to break up the neurotransmitter, AChE.

What is the NAChR?

NAChR stands for nicotinic acetylcholine receptor. There is more than one type of NAChR, especially depending upon where they are, but they do pretty much the same thing. The idea is that the receptor accepts a signal from a pre-synaptic neuron and converts it into an action-potential. In this way, the neuron passes on the signal, and the cell with the NAChR can carry this signal on.

If the cell receiving the signal is a muscle cell, then the NAChR has five subunits - known as 2 α, a β, a γ and a δ unit, with a channel in the middle. It is the alpha subunits that the acetylcholine binds to, opening the central channel and allowing cations to flow through. This will be addressed properly later.

If the cell receiving the signal is a neuron (i.e. one neuron is passing on a signal to another neuron) then the receptor is only made up of two subunits, but one of these is again an alpha unit, and it forms the binding site of ACh again.

Each of these subunits crosses the membrane completely, forming a complete channel that allows ions to travel all the way into the cell. In fact, each protein subunit is made up of a string of amino acids that crosses the membrane four times.

More and more is discovered about the nicotinic acetylcholine receptor all the time. It is interesting to know, however, that there is more than one kind of ACh receptor - the other broad family is known as the muscarinic ACh receptor, which are receptors used in a different part of the nervous system.

What is AChE?

AChE stands for acetylcholinesterase. It is the name given to an enzyme which breaks down the ester bond in acetylcholine, forming the two molecules acetic acid (or acetate) and choline.

The enzyme is essential in the function of nerve cells, because it gets rid of the excess ACh. In fact, the vast majority of the ACh released into the synapse by the nerve is broken down by AChE, and some of the products are taken back up into the nerve to be used again.

AChE is so effective that it very quickly gets rid of all of the ACh. This means that if the ACh goes for the receptor straight away, it will be broken down before it gets the chance. This makes sure that the post-synaptic receptor is only activated when the pre-synaptic nerve tells it to; the action potential is only stimulated in the post-synaptic nerve or muscle fibre when the pre-synaptic nerve passes on some ACh. If AChE didn't get rid of the ACh, it would keep on floating about and keep activating the receptor - there would be no control, and therefore nerves would be useless.

However, this will hopefully make more sense in a moment.

How is an AP signalled?

The signalling of an action potential is essentially very complicated, but understanding it is also very satisfying - and helpful, if other aspects of human physiology are to be properly understood. Initially it's important just to be fully aware of what's going on at the pre-synaptic bouton (that's the name given to the terminal end of the nerve, the bit which constitutes the pre-synaptic part of the connection).

It's important to remember that the whole point of the synapse is to effectively pass on the action potential. So the depolarization has travelled down the nerve and reached its bouton; it now needs to pass it on to the next cell. With the membrane depolarized, voltage-sensitive calcium channels in the membrane of the bouton are opened, allowing calcium to enter the cell.

Via a complex process, this calcium entry prompts vesicles, pre-packed with acetylcholine, to approach the pre-synaptic membrane for the ACh to be exported.

The bouton is filled with mitochondria for this energetically expensive process. When the membrane repolarizes, the calcium channels close, ceasing to stimulate vesicles to approach the membrane, and therefore preventing further ACh release.

The release of ACh and stimulation of the post-synaptic cell involves three very important steps, which will be outlined now. The first occurs at the pre-synaptic membrane, the second two occur at the post-synaptic membrane. These are:

1. Exocytosis
2. NAChR stimulation
3. ACh breakdown

Exocytosis involves the export of material from a cell, by the docking of vesicles with the cell membane. Basically, after calcium entry into the bouton has prompted vesicles to approach the pre-synaptic membrane, these vesicles dock with the membrane and open out into the synapse. The animation on the left shows a view as if from beneath the pre-synaptic membrane, with the vesicles opening out and tipping ACh over you.

To explain exocytosis simply is quite difficult. The best way is probably to remember those bubble toys you may have played with as a child; a small loop would be dipped into bubble-mixture, and be coated with a thin film of bubble mixture. As you blew into it, bubbles of air would form and break off. Imagine the reverse process, with bubbles returning to the thin film and emptying their contents of air onto you. This is what's happening in exocytosis.

The second process is activation of the nicotinic acetylcholine receptors. ACh, having just been released from the pre-synaptic membrane, is thrown onto the post-synaptic receptors on the other side of the synapse. The molecules of ACh then bind to the α units of the NAChR, causing the channel in the middle to open, and thereby allowing sodium to diffuse into the cell down a large concentration gradient.

The entrance of sodium into the cell causes the membrane to become depolarised, and an action potential is created. If this cell is a nerve, this can go on to stimulate whatever it is to stimulate; if this cell is a muscle, then the action potential will propogate along the membrane and cause the fibre to contract.

The third and final step to consider for now is the breakdown of ACh. Because the NAChR does not have a terribly high affinity for ACh, it soon breaks free. To stop this ACh from going to stimulate another receptor, a large concentration of AChE is present on the post-synaptic membrane to breakdown the excess ACh.

When AChE is broken down, its products don't go to waste. Some of the acetate and some of the choline are taken back up into the pre-synaptic bouton so that they can be joined together again, forming more ACh to be used at a later time.

Because it is important that ACh is quickly broken down to prevent unwanted re-stimulation, the concentration of AChE enzymes is very, very high. However, this means that a large amount of ACh must be released from the pre-synaptic cell in order to produce even a small response. Although this may seem wasteful, it is actually the only way of achieving a controlled response to the stimulus.

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