The Neuromuscular Junction and the Relationship between Drugs and Synapses.

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Greetings to the community and to all my readers. Thank you for the constant support and feedback. Still on Neurotoxin, Nerves, Neurons and Impulses; but today’s post will be a discussion on a special sort of synapse named the neuromuscular junction. It’s a continuation from where I stopped in my last post on COMMUNICATION BETWEEN NEURONS: THE SYNAPSE. Aside from talking about the neuromuscular junction, I will also explain the relationship between drugs and synapses. So, let’s ride on…..

A SPECIAL SORT OF SYNAPSE: The Neuromuscular Junction

When a motor neuron terminates on a muscle, it branches into many specialized synapses called neuromuscular junctions. The figure below shows a typical neuromuscular junction. These structures are wider than ordinary synapses and come into close contact with the surface membrane of the muscle, the sarcolemma. The area of sarcolemma in contact with the synapse is called the motor end-plate, and contains acetylcholine receptor sites. When an action potential arrives at a neuromuscular junction, vesicles of acetylcholine are released in the usual way. The transmitter changes the permeability of the motor end-plate to sodium ions and potassium ions, creating an end-plate potential (EPP) which results in an action potential passing along the sarcolemma. This impulse brings about the contraction of muscle fibres in that area.

Neuromuscular junction (closer view) 1. presynaptic terminal 2. sarcolemma 3. synaptic vesicles 4. Acetylcholine receptors 5. mitchondrion
Drawn by Dake, CC BY-SA 3.0

DRUGS AND SYNAPSES

Transmitters are released in tiny amounts: only 500-1000 molecules from each synaptic knob are required to transmit an impulse to a postsynaptic neuron. So, drugs that affect transmitters or their binding sites can have powerful effects when given in fairly small doses. Some chemicals, many of them from plants, have a dramatic effect on the nervous system.

NICOTINE AND ATROPINE

Nicotine is a substance found in tobacco. The nicotine molecule is a similar shape to acetylcholine and so competes with acetylcholine to bind with its receptors. Once the nicotine has bound to the receptor, it opens the sodium channel that forms part of the receptor, causing nerve impulses to be generated. Read the paragraph below for a discussion of the effects of nicotine.

Atropine also binds to acetylcholine receptors, but does not open the sodium channels. It blocks the receptors, and prevents acetylcholine binding to them. When this happens in motor neurons, it causes muscle paralysis.

Nicotine – the drug that mimics acetylcholine

Do you wonder why people continue to smoke, even though they know the increased risk of lung cancer and heart disease associated with their habit? The answer lies partly with one of the components of tobacco: nicotine.

Nicotine is very addictive. It affects the brains of smokers, making them feel less stressed, better able to concentrate and less likely to eat sweet foods. Smokers become tolerant to nicotine over time, needing to smoke more to achieve the same effects. But how does nicotine cause addiction?

Studies carried out in the early 1980s using nicotine labelled with a radioactive tracer showed that it is taken into the brain very rapidly. Once there, it binds tightly to acetylcholine receptors, fooling postsynaptic cells into ‘thinking’ they are being stimulated. It also binds to other receptors which nomally accept another neurotransmitter, dopamine.

The action of nicotine on both types of receptors in specific areas of the brain causes long-lasting changes to cell connections and may explain why it is addictive. We know that dopamine receptors, in particular, are involved in addictions to other substances such as mphetamines and cocaine.

Because nicotine is addictive but not carcinogenic (it is the chemicals in tobacoo tar that have been shown to cause cancer), smokers who are keen to kick the habit can get help. They can buy skin patches and gum that deliver nicotine to the brain but not tar to the lungs.

Although patches and gum do help smokers to cut down or stop smoking altogether, they are only a partial solution. Nicotine affects the acetylcholine receptors in the parasympathetic nervous system that are involved with the constriction of blood vessels. Over time, circulatory problems and heart disease can result, and it is best to avoid these effects altogether.

A 21 mg patch applied to the left arm. The Cochrane Collaboration finds that nicotine replacement therapy increases a quitter's chance of success by 50–60%, regardless of setting.
RegBarc, CC BY 2.5

DRUGS AND NORADRENALINE

Beta-blockers have a similar shape to noradrenaline and so compete with it for receptors on the postsynaptic membrane. Amphetamines and cocaine also affect noradrenaline synapses, but they work in a different way. They prevent the reabsorption of noradrenaline from the synaptic gap. So, noradrenaline remains in the gap and the neuron keeps on firing. An effect of amphetamines is to make a person feel energetic and carefree, which is why these substances are often known as speed. Before the harmful effects were known, amphetamines were given to pupils with poor attention spans, to help them concentrate.

Amphetamines are psychologically addictive. Users become dependent on the drug to avoid the ‘down’ feeling they often experience when the effect of the drug wears off. This dependence can lead a user to turn to stronger stimulants such as cocaine, or to larger doses of amphetamines to maintain a ‘high’.

People who abruptly stop using amphetamines often experience the physical signs of addiction, such as fatigue, long periods of sleep, irritability and depression. How severe and prolonged these withdrawal symptoms are depend on the degree of abuse.

MDMA (3,4-methylenedioxy-N-methamphetamine) is a long chemical name for what is commonly called Ecstasy, a recreational drug that is illegal in the UK. It works by boosting the release of the neurotransmitter serotonin, making people who take it feel well, relaxed, happy and more in tune with those around them, However, long-term use of the drug can cut down the number of serotonin receptors, leading to irreversible alterations in brain chemistry.

MDMA, Ecstasy drug
Ras67, public domain

Prozac and tranquilizers

Serotonin is a neurotransmitter normally active in the brain. Some forms of depression are caused by a reduced concentration of serotonin in the brain. The antidepressant drug Prozac is known as a serotonin re-uptake inhibitor. Prozac is said to alleviate depression because it competes with serotonin for the ‘active’ sites on the proteins that reabsorb serotonin, leading to a higher concentration of serotonin at synapses in the brain. It also competes for the active sites on the enzymes that break down serotonin at synapses.

Tranquilizers are drugs that reduce tension. Benzodiazepine tranquilizers, such as Valium, work by increasing the binding of inhibitory transmitters in the brain. Inhibitory transmitters hyperpolarize rather than depolarize the membrane of the next neuron. This makes the next neuron less excitable. Valium reduces stress and anxiety, but it can be addictive.

SUMMARY

When you have read this post and the previous ones such as NEUROTOXINS, NERVES, NEURONS AND IMPULSES, The Roles of Neurotoxins, Neurons, Nerves and Impulses #2, COMMUNICATION BETWEEN NEURONS: THE SYNAPSE and this final episode, you should know and understand the following:

  • The basic unit of the nervous system is the nerve cell, or neuron. This is a specialized cell with many dendrites that take impulses into the cell body, and a single, greatly elongated, axon that takes impulses away from the cell body.
  • The axon membrane is able to use an active transport mechanism to establish a resting potential. This is an electrical charge across the membrane caused by unequal distribution of ions.
  • The nerve impulse itself, called the action potential, is a momentary reversal in the resting potential, caused by a sudden rush of sodium ions into the axon. The action potential spreads rapidly along the axon.
  • The action potential lasts for only a millisecond or so, after which the resting potential is re-established. When an action potential has passed, there is a brief period of time – the refractory period – during which it is impossible to generate another action potential.
  • The nerve impulse passes from one neuron to another (or from a neuron to a muscle cell) by means of synapses.
  • Synapses are vital in selecting some neural pathways and not others. As such, synapses play a vital role in memory, skill and co-ordination of the body’s activities.
  • Transmission across synapses occurs when a chemical, the neurotransmitter, is released by the presynaptic membrane. This chemical diffuses across the gap and changes the permeability of the postsynaptic membrane, generating an excitatory postsynaptic potential (EPSP). If the EPSPs are sufficiently large, an action potential is generated in the next neuron.
  • Summation means that the effect of several action potentials can add up to produce transmission at a particular synapse.
  • Many drugs and poisons work by affecting synaptic transmission.

Thank you for coming.

REFERENCES

https://www.ncbi.nlm.nih.gov/books/NBK470413/
https://www.britannica.com/science/neuromuscular-junction
https://en.wikipedia.org/wiki/Neuromuscular_junction#:~:text=A%20neuromuscular%20junction%20
https://www.researchgate.net/publication/230209296_Drugs_and_the_Synapse
https://psych.athabascau.ca/html/Psych402/Biotutorials/13/part1.html
https://science.education.nih.gov/supplements/webversions/BrainAddiction/guide/lesson3-1.html#:~:text=One%20way%20to%20affect%20synaptic,they%20produce%20more%20action%20potentials.
https://onlinelibrary.wiley.com/doi/pdf/10.1002/jcp.1030130110
https://chem.libretexts.org/Bookshelves/Biological_Chemistry/Supplemental_Modules_
https://science.howstuffworks.com/nicotine3.htm
https://en.wikipedia.org/wiki/Norepinephrine
https://en.wikipedia.org/wiki/Norepinephrine
https://www.drugs.com/mtm/norepinephrine.html
https://en.wikipedia.org/wiki/MDMA
https://www.drugabuse.gov/publications/drugfacts/mdma-ecstasymolly
https://www.ncbi.nlm.nih.gov/pubmed/19524858
https://sunrisehouse.com/depression/antidepressants/fluoxetine/



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