The Roles of Neurotoxins, Neurons, Nerves and Impulses #2.

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Hello, dear reader. Still on Neurotoxin, Nerves, Neurons and Impulses where I last discussed about the Neurotoxins on the arrow tip, how information travels around the body, nerves; and how they carry information. But, today, I will be shedding more light on the action potential, myelinated neurons and saltatory conduction of nerves.

THE ACTION POTENTIAL

An action potential is generated when a nerve is stimulated. The stimulus may come from a receptor cell (e.g. in a sense organ) or another neuron. The action potential is brought about by a quick reversal in the permeability of the axon membrane that spreads rapidly down the axon as a wave of depolarisation. This allows sodium ions to flow suddenly into the axon, making the inside positive with respect to the outside. The sodium and potassium channels are voltage gated, which means that the can change their shape to let more or fewer ions pass, according to the voltage across the membrane.

When an action potential arrives at the end of the pre-synaptic axon (top), it causes the release of neurotransmitter molecules that open ion channels in the post-synaptic neuron (bottom). The combined excitatory and inhibitory postsynaptic potentials of such inputs can begin a new action potential in the post-synaptic neuron.
Thomas Splettstoesser, CC BY-SA 4.0

The action potential has two stages, depolarisation and repolarisation both of which are illustrated in the figure below:

Depolarisation step by step

  • When a neuron is stimulated, the voltage across the axon membrane changes.
  • A few voltage gated sodium channels detect this change and open to allow some sodium ions to diffuse in.
  • If the stimulus is large enough to reach the threshold value of about -50 mV, then the rest of the voltage gated sodium channels open for about 0.5 milliseconds.
  • This causes sodium ions to diffuse in very rapidly, making the inside of the cell more positive compared to the outside.
    This is an example of a positive feedback (‘change creating more change’). The more sodium ions there are, the more the voltage changes, so the more ion channels open, so the more sodium ions diffuse in.

Repolarisation

When the membrane potential reaches zero, the potassium channels open for 0.5 milliseconds, causing potassium ions to rush out, making the inside of the cell more negative again. Since this restores the original polarity, it is called repolarisation.

Re-establishing the resting potential

The potassium channels remain open until after the resting potential value of -70 mV has been reached. This causes hyperpolarisation (the ‘undershoot’ visible) when the potential difference reaches about -80 mV. The potassium channels then close and the resting potential is established once again.

The refractory period

Nerves conduct messages by firing repeated action potentials along the nerve fibres. The time delay between one action potential and the next is called the refractory period. This has two phases:

  • The absolute refractory period. During this time, immediately after the sodium channels close, no further impulse can be conducted.
  • The relative refractory period. During this time, the membrane begins to recover and becomes increasingly responsive. It is possible to initiate another action potential provided that the stimulus is greater than normal.

The refractory period imposes a limit on the frequency of nerve firing. Large nerve fibres recover in one millisecond and could theoretically propagate 1000 impulses per second. Small fibres take longer to recover about four milliseconds – and so could propagate about 250 impulses per second.

The refractory period ensures that each action potential is separated from the next, with no overlapping of signals. We can think of the information the signal conveys as coded information. The refractory period also ensures that a nerve impulse flows in one direction only: the wave of depolarisation can only move away from the refractory region, towards the axon terminal, and therefore onwards to the next neurone in the pathway.

The speed of an action potential

The speed at which a nerve impulse or action potential travels is known as its conduction velocity. In human nerve fibres, values range from one to three metres per second in unmyelinated fibres, and between three and 120 metres per second in myelinated fibres (see below for more information. In general, conduction velocity depends on the following factors:

  • Axon diameter. The larger the axon, the faster it conducts.
  • Myelination of the neurone. A nerve impulse travels faster in a myelinated nerve than in an unmyelinated nerve.
  • Number of synapses involved. Communication between neurones across the tiny gaps at the synapses involves chemical release and a brief time delay. The greater the number of synapses in a series of neurones, the slower the conduction velocity.

Membrane Permeability of a Neuron During an Action Potential
CThompson02, CC BY-SA 4.0

Remember that a nerve impulse is an all or nothing signal: if the threshold is not reached, depolarisation does not occur and no signal can travel along the axon. Also, generally speaking, myelination is rare in invertebrates. In order to speed up nerve transmission, the axon tends to get wider. It is thought that the giant axon of the squid evolved to speed up its escape reflex.

MYELINATED NEURONES AND SALTATORY CONDUCTION

Some nerves have exposed axon membranes but thers are covered in a sheath of fatty material called myelin. We have just seen, myelinated nerves conduct nerve impulses faster than unmyelinated nerves. This is an advantage as it allows information to travel around the body more quickly – this is probably why higher animals with more complex nervous systems – such as mammal – have many myelinated nerves. The detailed structure of a generalized myelinated motor neurone is shown below. The pale, creamy colour of myelinated nerves is due to the fatty (lipid) nature of the myelin that surrounds them.

The importance of myelin

But what is myelin and how does it form around neurons? Specialised cells called Schwann cells wrap themselves round the axons of some neurons as they develop in a growing embryo. The Schwann cells form a thick, lipid-rich insulating layer called the myelin sheath. This insulates the axon electrically, rather like the plastic layer round a copper wire in an electrical flex. Neurons with myelin sheaths are said to be myelinated.

Saltatory conduction

Saltatory conduction occurs in myelinated nerves, when the actíon potential ‘jumps’ from node to node. This greatly inereases the speed of signal transmission. The myelin sheath insulates the axon, and so ion exchange can only occur at the nodes of Ranvier in between the Sehwann cells, where the axon membrane is exposed.
The mechanism of saltatory conduction appears to be as follows:

  • When the action potential is present at one node, the influx of sodium ions causes the displacement ot potassium ions down the axon (like charges repel).
  • This diffusion of potassium down the axon makes the next node more positive and depolarises it until the threshold is reached.
  • The impulse quickly jumps by this mechanism from node to node at speeds of over 100 metres per second, ten times faster than the best sprinters. Saltatory conduction, from ‘saltare’ meaning to jump, refers to jumping conduction.
    As well as being faster than non-myelinated conduction, saltatory conduction is very energy efficient in terms of ATP usage. Only a small part of the axon is involved in the exchange of ions, so fewer ions need to be pumped back after the action potential has passed.

In saltatory conduction, an action potential at one node of Ranvier causes inwards currents that depolarize the membrane at the next node, provoking a new action potential there; the action potential appears to "hop" from node to node.
NickGorton~commonswiki, CC BY-SA 3.0

An autoimmune disease of the nerves

Multiple sclerosis (MS) is a chronic, often disabling disease of the central nervous system that is caused by a loss of myelin around neurones. Symptoms may be mild, such as numbness in the limbs, or severe -paralysis or loss of vision. Most people with MS are diagnosed between the ages of 20 and 40 but the unpredictable physical and emotional effects can be lifelong.

MS is classified as an autoimmune disease: it results from the immune system attacking the body’s own cells, mistaking them for foreign invading microbes. MS seems to be caused by a chemical found naturally in the body called inteferon gamma. This molecule usually helps to activate the immune system to attack viruses and bacteria and other infectious agents. In people with MS, interferon gamma causes the immune system wrongly to identify nerve cells as foreign invaders. As a result, the myelin sheath coating nerves in the brain and spinal cord is destroyed by mistake. Transmission between nerve cells slows down and also becomes erratic.

At the moment, there is no cure for MS but there are drugs that can reduce the symptoms and that can minimise the number of relapses and attacks that people with the condition suffer, In the UK, some drugs are approved for the treatment of MS. All work in much the same way – they block the damaging action of white cells that have been activated by the body’s own inteferon gamma, so reducing the attacks on myelin. These drugs can help reduce the symptoms, but they cannot reverse the changes that have already occurred.

I will pause here for now and continue in my next post, where I will discuss the communication between neurons i.e talking about the synapse, the main features of a chemical synapse and how the synapse works.

Thanks for reading

REFERENCES

https://teachmephysiology.com/nervous-system/synapses/action-potential/
https://www.ncbi.nlm.nih.gov/books/NBK11146/
https://www.britannica.com/science/action-potential
https://en.wikipedia.org/wiki/Action_potential
https://www.news-medical.net/health/Myelin-Function.aspx
https://www.ms-society.ie/sites/default/files/2019-05/what%20is%20ms%20importance_myelin.pdf
https://en.wikipedia.org/wiki/Saltatory_conduction
https://www.mstrust.org.uk/about-ms/ms-treatments/disease-modifying-drugs-dmds
https://www.nhs.uk/conditions/multiple-sclerosis/treatment/
https://www.foundationforpn.org/what-is-peripheral-neuropathy/causes/autoimmune-disease/
https://www.webmd.com/brain/qa/how-do-autoimmune-diseases-cause-nerve-damage



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Nice job finding a way to easily explain something as complex as depolarization and repolarization

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