We all know that any sort of movement which is happening inside the body is completely regulated through the nervous system. But many of us are not aware of the accurate mechanism of it. They are completely unaware of the connection which is taking place between the muscular system and nervous system.
Introduction about Neuromuscular Junction
As it is evident from the name, it is working as the bridge which is taking place between the muscular system and nervous system. It is a form of microstructure that is all carried out through the contraction process, which is halted into the muscles by the help of neurons. Any sort of changes that takes place inside the neuromuscular junction can often result in the impaired-based contractions of skeletal muscles.
Here we will have a quick guide about how the whole structure of the neuromuscular junction has been taking place and how this whole mechanism is working. We will also explain the drug action on it along with the clinical significance.
Structure of Neuromuscular Junction
This entire Neuromuscular Junction is a form of chemical synapse which is happening between the motor neuron as well as skeletal muscle fibre. It is included with the presynaptic terminal, or synaptic cleft, as well as postsynaptic membrane or cell.
Given the Neuromuscular Junction, the whole scenario of the presynaptic terminal is a form of the axonal terminal of a set of motor neurons. The axonal terminal is based on the number of synaptic vesicles. These all vesicles are put together with the neurotransmitters that are somehow released upon by receiving a nerve impulse.
The presynaptic terminal is also finished with the calcium channels. All such channels are the voltage-gated calcium-based channels that will open through the nerve impulse as it reaches into the presynaptic axonal terminal.
It is a space that is happening as in between the presynaptic terminal as well as the postsynaptic cell. It has a size of around 30mm. This whole element will allow the basic neurotransmitters to completely diffuse and hence make its way to the other side of the synapse or Neuromuscular Junction. Plus it is also included with the enzymes meant for the degradation of extra neurotransmitters. Any sort of changes that take place inside the neuromuscular junction can often result in the impaired based contractions of skeletal muscles.
Post Synaptic Cell or Membrane
The whole course of postsynaptic cells in the process of Neuromuscular Junction is the skeletal muscle fibre. The whole set of motor neurons somehow make the synapse on top of the sarcolemma or the membrane of the skeletal muscle fibres.
By the side of the neuromuscular junction, the set of the sarcolemma of the skeletal muscle will start to display a series of invaginations which is known as postjunctional folds. These all folds will increase the overall surface area in which the transmitters will act.
All the walls of these basic folds have acetylcholine receptors. These all receptors are known to be the most important part of the neuromuscular junction.
Details of the receptors are discussed below:
- Acetylcholine Receptors
Acetylcholine is one such neurotransmitter which is utilized in the neuromuscular junction. You can find such receptors inside the walls of the post-junctional folds. They have also been known by the name cholinergic receptors. Hence these receptors can also be activated through nicotine which is known as nicotinic receptors.
These acetylcholine receptors are working as the ionotropic receptors, which are associated with the ion channels. They are made out of two α, one β, one ɛ, and one δ subunit. The set of acetylcholine simply binds itself towards the alpha subunit. Once the single acetylcholine molecule fully binds towards the alpha subunit, it simply induces a series of conformational changes which is resulting in increasing the affinity of the second subunit.
As both of the subunits occupy themselves by the acetylcholine, it eventually results in the opening of the cation channels. This will be resulting in the inward diffusion of sodium as well as potassium ions.
- Mechanism of Contraction
As the nerve impulse will be reaching towards the presynaptic axonal terminal, it might start causing depolarization. As a result of it, the voltage-gated calcium channels will open up. All the calcium ions from the overall surrounding environment will diffuse into the presynaptic axon.
These calcium ions will activate the SNARE proteins. These all proteins hence mediate the overall fusion of the synaptic vesicles to the cell membrane of the neuron, which will be resulting in the release of acetylcholine into the synaptic cleft.
As soon as the acetylcholine is all released into the course of the synaptic cleft, it hence diffuses all across the synaptic cleft and yet binds towards the acetylcholine receptors. This hence results in the opening of various cation channels. These channels are completely open to both sodiums as well as potassium ions.
Normally the overall concentration of the sodium ions is very much high within the extracellular space where the sodium ions somehow enter through these all open cation channels. This will result in the depolarization of skeletal muscle ensues.
This condition of depolarization of the sarcolemma will be resulting in the opening of voltage-gated calcium channels which are positioned at the sarcolemma and membrane of the smooth endoplasmic reticulum.
Drugs Acting on Neuromuscular Junction
The entire functioning and overall normal mechanism of the neuromuscular junction is fully affected through the below-mentioned drugs:
- Cholinergic Drugs
These drugs increase the amount of acetylcholine within the synaptic cleft. There are two main types which are direct-acting and indirect-acting
- Direct Acting Drugs
These sorts of drugs will be increasing the overall amount of acetylcholine using acting as its precursor. These will include bethanechol, methacholine, etc.
- Indirect Acting Drugs
You can make them known to be the inhibitors of acetylcholinesterase enzymes. They simply inhibit the metabolism of acetylcholine that results in the increased amount of the acetylcholine towards the synaptic cleft. These drugs will include neostigmine, physostigmine, etc.