In this article we are going to answer the question ‘’What is a neuromuscular junction?’’ we will explain how the muscles communicate with the brain.
What is a neuromuscular junction?
The neuromuscular junction is the site where the synapse between the nervous system and the muscle occurs and is constituted by:
- The lower motor neuron whose axon travels along a peripheral nerve and terminates at the presynaptic terminal of the neural plate.
- The synaptic cleft.
- The muscle cells whose membrane constitutes the postsynaptic terminal.
The process of muscle contraction begins with the electrical signal that comes from the spinal cord, and travels along the axonal membrane to the presynaptic terminal. At this point it activates the calcium channels, leading to the release of acetylcholine into the synaptic cleft.
Once the acetylcholine is released, it binds to postsynaptic receptors inducing the massive opening of calcium channels. Finally, the massive entry of calcium into the muscle cell activates the proteins that produce contraction (actin, myosin…).
Generically, pathologies affecting the neuromuscular junction can compromise the presynaptic release of acetylcholine, as in botulism or Eaton-Lambert syndrome, or the activation of postsynaptic receptors, as in the case of myasthenia gravis.
Once the motor plate is depolarized, the action potential runs through the entire sarcolemma (muscle cell membrane).
The action potential of a muscle fiber is divided into several phases: phases 0 and 1 correspond to depolarization due to sodium entry; phase 2, also called plateau, is due to slow calcium entry; phase 3 is due to repolarization due to potassium exit and finally phase 4 with sodium exit and potassium entry back into the cell.
The release of additional calcium accumulated in the sarcoplasmic reticulum is adduced to calcium. This calcium diffuses to the sarcomeres, i.e. to all the contractile proteins. It first binds to troponin and thus produces a change in the conformation of tropomyosin. This modification in turn exposes actin to the interaction of myosin.
This binding, in the presence of ATP and magnesium molecules, produces shape-changing bridges that are able to slide the actin over the myosin. This produces a shortening of the sarcomeres and thus muscle contraction.
Relaxation or recovery of the initial position is produced by the breakage of these bridges upon rotation, releasing ADP. During repolarization of the sarcolemma the sarcoplasmic reticulum recovers calcium thanks to an energy consumption system (ATP).
Neuromuscular diseases are a group of more than 150 hereditary or acquired neurological diseases that affect the musculature and the nervous system.
They belong to the group of so-called rare diseases, being little known diseases.
Their onset can occur at any stage of life, whether at birth, adolescence or adulthood.
Neuromuscular diseases are chronic diseases, that is to say, once their effects appear, they last for life.
Most neuromuscular diseases are progressive in nature. This type of evolution causes those affected to see their functional capacity diminished and, with it, their personal autonomy to carry out daily tasks. This results in increasing physical dependence on a third person, adaptations or assistive devices.
There is currently no etiological treatment, so rehabilitation strategies are essential in order not to cure the disease, but to prevent its complications, and thus try to reduce disability and improve the quality of life of these people.
Symptoms of neuromuscular diseases
Their most important symptom is the loss of muscle strength, which can be present from birth or appear slightly at any age.
Neuromuscular diseases are chronic diseases, that is to say, once they begin to show their symptoms they last a lifetime.
They are progressive or neurodegenerative diseases, due to the involvement of muscles or associated nerves.
This loss of strength limits aspects of social and emotional life, etc., and especially produces a feeling of dependence on others.
Although there are high hopes for an effective treatment for the vast majority of these diseases, it does not exist at present. However, rehabilitation treatment is essential for maintaining the functional capacities and quality of life of those affected.
What diseases affect the motor plate?
The neuromuscular plate plays an essential role in making the connection between the nerve and the end plate of the effector muscle, and this can be seriously affected in diseases such as myasthenia gravis and botulism.
Myasthenia gravis is a disease caused by a defect in the transmission of nerve impulses to the muscles, the immune system through antibodies blocks, alters and destroys the acetylcholine receptors located in the neuromuscular junction, preventing muscle contraction.
The thymus is a gland that is an important part in the development of the immune system, in patients suffering from this disease this gland generates an abnormal function, producing incorrect actions in the antibodies.
Another relevant disorder in which symptoms are largely due to problems in the neuromuscular plate is botulism. In this disease, an alteration is generated due to the presence of botulinum toxin that prevents acetylcholine from binding to other substances that allow its excretion from the presynaptic membrane.
Known as the most potent poison, Botulinum Toxin causes muscle paralysis and can even kill if accidentally ingested in contaminated food. However, after investigating the mechanism it uses to paralyze muscles, it has been found that this terrible poison, in very low doses, can alleviate or cure disorders in which a muscle is overactive.
A disease in which the immune system affects the calcium pathways present in motor neurons. This leads to blocking and hindering the emission of acetylcholine in the synaptic space, which ends up generating a high level of fatigue and muscle weakness, both voluntary and neurovegetative.
Eaton-Lambert syndrome is a disorder with symptoms very similar to those of myasthenia gravis, in which there is muscle weakness related to the blockage of myoneural communication.
The syndrome was described by Lealdes McKendre Eaton and Edward Howard Lambert, both of whom were professors of Neurology at Mayo Clinic and devoted their research to myasthenia gravis, polymyositis, neurophysiology and electrophysiology.
Paraneoplastic syndromes are symptoms that appear in locations distant from a tumor or its metastases. They can occur in any organ or physiological system.
These symptoms are most commonly associated with certain types of cancer, such as lung cancer, leukemia or breast cancer. The treatment of paraneoplastic syndrome is linked to cancer that causes it, although some symptoms can be controlled by the administration of drugs.
Some general symptoms of paraneoplastic syndrome are fever, night sweats or cachexia. Also relatively frequent are skin symptoms, such as spots and itching (pruritus), and endocrine and digestive symptoms, such as glycemic alterations or diarrhea.
So, how does the neuromuscular junction work?
For the neuromuscular junction to work properly, it is necessary that 3 structures are working together, these are the neuron with motor characteristics that are responsible for sending the nerve impulse and that has the acetylcholine, then the synaptic space where the acetylcholine is released and finally the motor junction that belongs to the muscle fiber.
Another important structure is the synaptic button that has the motor neuron, through which acetylcholine is released.
Once all these structures are in place, the process of muscular contraction begins, and this can only occur thanks to the presence of calcium.
The physiology of the neuromuscular junction is as follows:
- It begins with a resting potential that becomes an action potential.
- Thanks to the action potential, the neurotransmitter called acetylcholine is released.
- Once there is enough acetylcholine, depolarization occurs with the axon end plate potential.
- And this is how the muscle fibers are activated and contraction is generated.
What did you think about this article? If you have any questions or comments please let us know!
Witzemann, V. (2006). Development of the neuromuscular junction. Cell and tissue research, 326(2), 263-271.
Engel, A. G. (2008). The neuromuscular junction. Handbook of Clinical Neurology, 91, 103-148.
Hirsch, N. P. (2007). Neuromuscular junction in health and disease. British journal of anaesthesia, 99(1), 132-138.