Neuromuscular Connection | Structure, function, summary and clinic (2023)

Many people know that any movement made by the body isregulated by the nervous system. But most of them don't know the exact mechanism of how it happens. They are not aware of the connection between the nervous system and the muscular system.

The neuromuscular junction, as its name implies, acts as a bridge between the nervous system and the muscular system. It is a microstructure through which neurons start or stop the contraction process in muscles. Any change inneuromuscular junctionmay result in compromiseskeletal muscle contractions.

In this article we will study in detail the structure of the neuromuscular junction, the mechanisms by which it initiates the contraction mechanism, the drugs that act on it, as well as its clinical significance. By the end of this article, you will be able to understand the process of how contraction is initiated by theneuromuscular junction.

Structure

Oneuromuscular junctionIt is a chemical synapse between the motor neuron and the skeletal muscle fiber. It consists of a presynaptic terminal, a synaptic cleft, and a postsynaptic cell or membrane.

presynaptic terminal

In the case of the neuromuscular junction, thepresynaptic terminalIt is an axonal terminal of a motor neuron. The axon terminal contains several synaptic vesicles. These vesicles contain the neurotransmitters that are released when receiving a nerve impulse.

The presynaptic terminal also has calcium channels. These channels are voltage-gated calcium channels that open when a nerve impulse reaches the presynaptic axon terminal.

synaptic cleft

It is the space between the presynaptic terminal and
the postsynaptic cell. It is approximately 30 nm in size. the synaptic cleft
allows neurotransmitters to diffuse and reach the other side of the synapse
or the neuromuscular junction. It also contains enzymes for the degradation of
the excess or excess of neurotransmitters.

Cell or postsynaptic membrane

Opostsynaptic cellin the case of the neuromuscular junction is theskeletal muscle fiber. Motor neurons synapse on the sarcolemma, or membrane, of skeletal muscle fibers.

At the neuromuscular junction, the sarcolemma of skeletal muscle displays a series of invaginations called postsynaptic folds. These folds greatly increase the surface area on which neurotransmitters act.

The walls of these folds haveacetylcholine receptors. These receptors are the most important functional part of the neuromuscular junction. A brief detail of these receptors is provided below.

Acetylcholine receptors

Acetylcholine is the neurotransmitter used at the neuromuscular junction. Acetylcholine receptors are present in the walls of thepostunion folds. These receptors are also called cholinergic receptors. The receptor can also be activated by nicotine, so they are called nicotinic receptors.

Oacetylcholine receptors are the ionotropic receptors linked to ion channels. It is composed of two α subunits, one β, one ɛ and one δ. Acetylcholine binds to the alpha subunit. when a singleacetylcholine moleculebinds to the alpha subunit, it induces a conformational change that results in a higher affinity of the second subunit.

When both subunits are occupied by acetylcholine,opening of cation channels, resulting in internal diffusion of sodium and potassium ions.

contraction mechanism

When a nerve impulse reaches the presynaptic axon
terminal, causes depolarization. As a result, the voltage-dependent calcium
open channels. Calcium ions from the surrounding environment diffuse
the presynaptic axon.

These calcium ions activate the SNARE proteins. Those
Proteins mediate the fusion of synaptic vesicles with the cell membrane of the
neuron, resulting in the release of acetylcholine into the synaptic cleft.

Since acetylcholine isreleased into the synaptic cleft, diffuses through the synaptic cleft and binds to acetylcholine receptors. This results in the opening of the cation channels. These channels are open to sodium and potassium ions.

Since the concentration of sodium ions is higher in the
Into the extracellular space, sodium ions enter through these open cation channels.
As a result, depolarization of skeletal muscle occurs.

Odepolarization of the sarcolemmait results in the opening of voltage-gated calcium channels located in the sarcolemma, as well as in the smooth endoplasmic reticulum membrane.

while thecalcium ionsentering the cell, it initiates the skeletal muscle contraction cycle. Actin-myosin bridges are formed and result in the contraction of skeletal muscles.

Once acetylcholine is released at the synapse
cleavage, has a very short half-life. It is immediately metabolized by
acetylcholinesterase to its metabolites. The hill thus formed is absorbed by
presynaptic neurons. Metabolism of acetylcholine to its metabolites
results in the removal of all its effects and muscle contraction
it stops

Drugs acting at the neuromuscular junction

The normal mechanism and function of the neuromuscular
union is affected by the following drugs.

cholinergic drugs

These drugs increase the amount of acetylcholine in the
the synaptic cleft. There are two types, direct action and indirect action.
cholinergic drugs.

Direct acting drugs

These drugs increase the amount of acetylcholine by acting as its precursor. These includebetanecol,metacolina, etc.

Indirect acting drugs

These are acetylcholinesterase inhibitors.
enzyme. They inhibit the metabolism of acetylcholine, resulting in a
increased amount of acetylcholine in the synaptic cleft. These drugs include
neostigmina, fisostigmina, etc.

neuromuscular blockers

These are the antagonists ofnicotinic acetylcholine receptorspresent at neuromuscular junctions. Blockade of these receptors results in relaxation of skeletal muscles. These drugs are used as skeletal muscle relaxants.

They are further divided into two types,
nondepolarizing and nondepolarizing.

non-depolarizing drugs

These drugs are antagonists ofnicotinic receptors. They block receptors and prevent depolarization, resulting in skeletal muscle relaxation. These drugs have few side effects and are used more often than depolarizing drugs. These include atracurium, tubocurarine, etc.

Depolarizing Medications

These drugs are potent nicotinic receptor agonists. They cause excessive depolarization, which cannot be reversed. Prolonged depolarization causes A1 blockade, resulting inrelaxation of skeletal muscles. These include suxamethonium and other drugs.

clinical significance

Important clinical conditions associated with
neuromuscular junction are as follows.

Myasthenia gravis

It's aautoimmune diseasein which antibodies are formed against acetylcholine receptors. As a result, the neuromuscular junction is unable to initiate skeletal muscle contraction.

This results in varying degrees of muscle weakness. The muscles most commonly affected include the muscles of the eyes, face, and pharynx that help with swallowing.

Lambert-Eaton Syndrome

and otherautoimmune diseaseof the neuromuscular junction. However, it affects presynaptic neurons. In this disease, antibodies are formed against voltage-gated calcium channels present on presynaptic neurons. TO

As a result, the nerve impulse arriving at the presynaptic terminal fails to release the neurotransmitter into the synaptic cleft. The muscles are unable to contract. It also causes varying degrees ofskeletal muscle weakness.

The most commonly affected muscles include those of the legs and arms. The person has trouble walking, climbing stairs, etc.

neuromiotonía

This disease of the neuromuscular junction produces hyperarousal of skeletal muscles. It is due to the downward regulation ofvoltage-gated postsynaptic potassium channels.

As a result, potassium ions are unable to leave skeletal muscle and hyperpolarization occurs. This hyperpolarization leads to hyperarousal of skeletal muscle and muscle spasm. It is also believed to be an autoimmune disorder of the neuromuscular junction.

Conclusion/Summary

neuromuscular junctionIt is a microstructure present at the junction of motor neurons with skeletal muscle fibers. It acts as a bridge connecting the skeletal system and the nervous system.

The neuromuscular junction is a chemical synapse.

The presynaptic terminal is the axonal terminal of the
motor neuron containing synaptic vesicles.

These vesicles are released into the synaptic cleft.
when a nerve impulse arrives.

The postsynaptic sarcolemma has the synaptic clefts
have acetylcholine receptors on their walls.

Oacetylcholine moleculesReleased from the presynaptic terminal, they bind to these receptors and cause the opening of cation channels.

Sodium ions diffuse through these channels,
resulting in depolarization of skeletal muscles. This depolarization initiates
the process of muscle contraction.

Acetylcholine is rapidly metabolized by
acetylcholinesterase, which eliminates all its effects.

The normal mechanism of the neuromuscular junction is
affected by cholinergic drugs, as well as skeletal muscle relaxants.

Ocholinergic drugs, which can be of direct or indirect action, increase the activity of acetylcholine.

Skeletal muscle relaxants areneuromuscular blockers. They block the neuromuscular junction by inhibiting depolarization or causing excessive depolarization.

The important pathological conditions associated with
the neuromuscular junction include:

• Myasthenia gravis
• Lambert-Eaton Syndrome
• neuromiotonía

These are all autoimmune conditions. the first two
result in muscle weakness, while the third causes hyperextension of skeletal muscles
muscles.

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