Neuromuscular Junction Notes

Neuromuscular Junction Definition And Structure

• Neuromuscular Junction Definition: Neuromuscular junction is the junction between the terminal branch of the nerve fiber and the muscle fiber.
• Neuromuscular Junction Structure: Skeletal muscle fibers are innervated by the motor nerve fibers. Each nerve fiber (axon) divides into many terminal branches. Each terminal branch innervates one muscle fiber through the neuromuscular junction.

Read And Learn More: Medical Physiology Notes

• • Axon Terminal and Motor End Plate: Terminal branch of the nerve fiber is called the axon terminal. When the axon comes close to the muscle fiber, it loses the myelin sheath. So, the axis cylinder is exposed. This portion of the axis cylinder is expanded like a bulb which is called the motor endplate.
  • Synaptic Trough or Gutter: The motor end plate invaginates inside the muscle fiber and forms a depression which is known as a synaptic trough or synaptic gutter. The membrane of the muscle fiber below the motor endplate is thickened.
  • Synaptic cleft:
    • The membrane of the nerve ending is called the pre-synaptic membrane. The membrane of the muscle fiber is called the postsynaptic membrane. The space between these two is called the synaptic cleft.
    • The axon terminal contains mitochondria and synaptic vesicles. The synaptic vesicles contain the neurotransmitter sub – stance, acetylcholine. The acetylcholine is synthesized by mitochondria present in the axon terminal and stored in the vesicles. The mitochondria contain ATP, which is the source of energy for the synthesis of acetylcholine.
    • The synaptic cleft contains basal lamina. It is a thin layer of spongy reticular matrix through which, the extracellular fluid diffuses. A large quantity of an enzyme called acetylcholinesterase is attached to the matrix of the basal lamina.
  • Subneural Clefts: The postsynaptic membrane is the membrane of the muscle fiber. It is thrown into numerous folds called sub neural clefts. The postsynaptic membrane contains the receptors called nicotine acetylcholine receptors

Neuromuscular Transmission

Neuromuscular transmission is defined as the transfer of information from the motor nerve ending to the muscle fiber through the neuromuscular junction. It is the mechanism by which the motor nerve impulses initiate muscle contraction. A series of events take place in the neuro-muscular junction during this process.

1. Release of acetylcholine
2. Action of acetylcholine
3. Development of endplate potential
4. Development of miniature endplate potential
5. Destruction of acetylcholine.

1. Release Of Acetylcholine:

• When the action potential reaches the axon terminal, it increases the permeability of the presynaptic membrane for calcium ions by opening the voltage-gated calcium channels in the membrane of the axon terminal. Calcium ions enter the axon terminal from the extracellular fluid. The calcium ions cause bursting of the vesicles.
• Actually, the calcium ions make the synaptic vesicles move and fuse with the presynaptic membrane. Now, acetylcholine is released from the vesicles. This process is called exocytosis. The acetylcholine diffuses across through the presynaptic membrane and enters the synaptic cleft.
• Each vesicle contains about 10,000 acetylcholine molecules. And, at a time, about 300 vesicles open and release acetylcholine.

2. Action Of Acetylcholine:

• After entering the synaptic cleft, the acetylcholine molecules bind with nicotinic receptors present in the postsynaptic membrane and form the acetylcholine-receptor complex.
• It opens the ligand-gated channels for sodium in the postsynaptic membrane. Now, sodium ions from extracellular fluid enter the neuromuscular junction through these channels. And there, the sodium ions produce an electrical potential called the endplate potential.

3. Endplate Potential: Endplate potential is the change in the resting membrane potential when an impulse reaches the neuromuscular junction. The resting membrane potential at the neuro-muscular junction is -90 mV. When sodium ions enter inside, slight depolarization occurs up to -60 mV which is called endplate potential.

• Properties of Endplate Potential: The endplate potential is a graded potential and it is not an action potential.
• Significance of Endplate Potential: The endplate potential is nonpropagative. But it causes the development of action potential in the muscle fiber.

4. Miniature Endplate Potential:

• Miniature endplate potential is a weak endplate potential in the neuromuscular junction that is developed by the release of a small quantity of acetylcholine from the axon terminal. And, each quantum of this neurotransmitter produces a weak, miniature endplate potential. The amplitude of this potential is only up to 0.5 mV.
• Miniature endplate potential cannot produce an action potential in the muscle. When more and more quanta of acetylcholine are released continuously, the miniature endplate potentials are added together and finally produce endplate potential resulting in an action potential in the muscle.

5. Fate Of Acetylcholine:

• Acetylcholine released into the synaptic cleft is destroyed very quickly. Within one millisecond after the release into the synaptic cleft, it is destroyed by the enzyme, acetylcholinesterase. However, the acetylcholine is so potent, that even this short duration of 1 millisecond is sufficient to excite the muscle fiber.
• The rapid destruction of acetylcholine has got some important functional significance. It prevents the repeated excitation of the muscle fiber and allows the muscle to relax.
  • Reuptake Process:
    • Reuptake is a process in neuromuscular junction, by which a degraded product of neurotransmitter re-enters the presynaptic axon terminal where it is reused. Acetyl-cholinesterase splits (degrades) acetylcholine into inactive choline and acetate.
    • Choline is taken back into the axon terminal from the synaptic cleft by the reuptake process. There, it is reused in synaptic vesicles to form new acetylcholine molecules.

Neuromuscular Blockers

Neuromuscular blockers are drugs, which can prevent the transmission of impulses from nerve fiber to the muscle fiber through the neuromuscular junctions. Following are some of the important neuromuscular blockers, which are commonly used, in clinical practice and in research.

1. Curare: Curare or the active principle of curare d-tubocurarine prevents neuromuscular transmission by combining with acetylcholine receptors. So, the acetylcholine cannot combine with the receptors. And, the endplate potential cannot develop. Since curare blocks the neuromuscular transmission by acting on the acetylcholine receptors, it is called a receptor blocker.
2. Bungarotoxin: It is a toxin from the venom of deadly snakes. It affects the neuromuscular transmission by blocking the acetylcholine receptors.
3. Succinylcholine and Carbamylcholine: These drugs block neuromuscular transmission by acting like acetylcholine and keeping the muscle in a depolarized state. But, these drugs are not destroyed by cholinesterase. So, the muscle remains in a depolarized state for a long time.
4. Botulinum Toxin: It is derived from the bacteria Clostridium botulinum. It prevents the release of acetylcholine from the axon terminal into the neuromuscular junction.

Drugs Stimulating Neuromuscular Junction

The neuromuscular junction can be stimulated by some drugs like neostigmine, physostigmine, and isopropyl fluorophosphate. These drugs inactivate the enzyme, acetylcholinesterase. So, the acetylcholine is not hydrolyzed. It leads to repeated stimulation and continuous contraction of the muscle.

Motor Unit

• Motor Unit Definition: The single motor neuron, its axon terminals, and the muscle fibers innervated by it are together called motor units. Each motor neuron activates a group of muscle fibers through the axon terminals. Stimulation of a motor neuron causes contraction of all the muscle fibers innervated by that neuron.
• Number Of Muscle Fibers In Motor Unit: The number of muscle fibers in each motor unit varies The number of muscle fibers is small in the motor unit of the muscles concerned with fine, graded and precise movements. Examples are:
  • Laryngeal muscles: 2-3 muscle fibers per motor unit
  • Pharyngeal muscles: 2-6 muscle fibers per motor unit
  • Ocular muscles : 3-6 muscle fibers per motor unit

The muscles concerned with crude or coarse movements have motor units with a large number of muscle fibers. There are about 120-165 muscle fibers in each motor unit in these muscles. Examples are the muscles of the leg and back.

• Recruitment Of Motor Units:
  • While stimulating the muscle with weak strength, only a few motor units are involved. When the strength of the stimulus is increased, many motor units are put into action. So, the force of contraction increases.
  • The process is by which more and more motor units are put into action is called the recruitment of motor units. Thus, the graded response in the muscle is directly proportional to the number of motor units activated.
  • The activation of motor units can be studied by electromyography.

Applied Physiology Disorders Of Neuromuscular Diseases

The disorders of neuromuscular junction include

1. Myasthenia gravis
2. Eaton-Lambert syndrome

1. Myasthenia Gravis: Myasthenia gravis is an autoimmune disorder of neuro-receptors.  Muscular junction caused by antibodies to cholinergic Receptors.

2. Eaton-Lambert Syndrome: Eaton-Lambert syndrome is also an autoimmune disorder of the neuromuscular junction. It is caused by antibodies to calcium channels in the axon terminal.