Neuromuscular junction ppt

1. Neuromuscular Junction
Dr. E. Muralinath, Dr. C. Kalyan Chakravarthi, Dr. M.
Guruprasad, Dr. K. Sravani Pragna, Dr. P. Manjari,
Dr. D. Kusumalatha, Dr. K. Sridevi , Dr. Ch. Ramya
Sudha and Dr. R. Gnana Lahari

2. • DEFINITION
• Neuromuscular junction is the junction between terminal branch of the nerve fiber and muscle fiber.
• STRUCTURE
• Skeletal muscle fibers are innervated by the motor nerve fibers.
• Each nerve fiber (axon) categorizes into many terminal branches.
• Each terminal branch innervates one muscle fiber through the neuromuscular junction
• .

3. • Axon Terminal and Motor Endplate
• Terminal branch of nerve fiber is otherwise known as axon terminal.
• When the axon comes close to muscle fiber, it loses the myelin sheath.
• So, the axis cylinder is disclosed.
• This portion of the axis cylinder is extended like a bulb, which is also termed as motor endplate.
• Axon terminal consists of mitochondria and synaptic vesicles.
• 6)Synaptic vesicles consist of the neurotransmitter substance, acetylcholine (Ach).
• 7)The synthesis of Ach takes place by mitochondria present in the axon terminal and stored in the
vesicles.
• 8) Mitochondria consist of ATP, which is the source of energy for the synthesis of acetylcholine.

4. • Synaptic Trough or Gutter
• Motor endplate invaginates inside the muscle fiber and forms a depression, which is also termed as
synaptic trough or synaptic gutter.
• The membrane of the muscle fiber below the motor endplate shows thickness..
•
• Synaptic Cleft
• Membrane of the nerve ending is otherwise known as the presynaptic membrane.
• Membrane of the muscle fiber is termed as postsynaptic membrane.
• Space between these two membranes is termed as synaptic cleft.
• Synaptic cleft consists of basal lamina. It is a thin layer of spongy reticular matrix through which,
the diffusion of extracellular fluid happens..
• An enzyme called acetylcholinesterase (AchE) is bound with the matrix of

5. • Subneural Clefts
• Postsynaptic membrane is the membrane of the muscle fiber.
• It is thrown into numerous folds termed as subneural clefts.
• Postsynaptic membrane consists of the receptors known as nicotinic acetylcholine receptors .
•
• NEUROMUSCULAR TRANSMISSION
• Definition
• Neuromuscular transmission is elucidated as the transfer of information from motor nerve ending
to the muscle fiber via neuromuscular junction.
• It is the mechanism
• by which the motor nerve impulses commence muscle contraction.

6. • Events of Neuromuscular Transmission
• A series of events take place in the neuromuscular junction during this process . The events are:
• 1. Release of acetylcholine
• 2. Action of acetylcholine
• 3. Development of endplate potential
• 4. Development of miniature endplate potential
• 5. Destruction of acetylcholine.

7. • 1. RELEASE OF ACETYLCHOLINE
• a)If action potential attains axon terminal, it opens the voltage-gated calcium channels in the
membrane of axon terminal.
• b) Calcium ions from extracellular fluid (ECF) gain an entry into the axon terminal.
• c)These cause rupturing of the vesicles by forcing the synaptic vesicles move and fuse with
presynaptic membrane.
• d)Now, the release of acetylcholine takes place from the ruptured vesicles.
• e)By exocytosis, acetylcholine diffuses through the presynaptic membrane and enters the synaptic
cleft.
• f)Each vesicle consists of approximately 10,000 acetylcholine molecules. And, at a time, about 300
vesicles open and release acetylcholine.

8. • 2. ACTION OF ACETYLCHOLINE
• a)After entering the synaptic cleft, acetylcholine molecules unite with nicotinic receptors present in
the postsynaptic membrane and form acetylcholine-receptor complex.
• b)It enhances the permeability of postsynaptic membrane for sodium by opening the ligand-gated
sodium channels.
• c) Now, sodium ions from ECF enter the neuromuscular junction through these channels. And there,
sodium ions alter the resting membrane potential and develops the electrical potential termed as the
endplate potential.

9. • 3. DEVELOPMENT OF ENDPLATE POTENTIAL
• a)Endplate potential is the change in resting membrane potential if an impulse enters the
neuromuscular junction.
• b) Resting membrane potential at neuromuscular junction is –90 mV.
• c)If sodium ions enter inside, light depolarization happens up to –60 mV, which is known as
endplate potential.
• Properties of Endplate Potential
• Endplate potential is a graded potential and it is not action potential.
• Miniature endplate potential cannot elicit action potential in the muscle.
• If more and more quanta of acetylcholine are released in a continuous manner, the miniature
endplate potentials are added together and finally initiate endplate potential leading to action
potential in the muscle.
•

10. • . DESTRUCTION OF ACETYLCHOLINE
• a)Acetylcholine released into the synaptic cleft is broken downin a very quick manner, within one millisecond by the
enzyme, acetylcholinesterase.
• b) Whatever it may be, the acetylcholine is so potent, that even this short duration of 1 millisecond is enough to excite the
muscle fiber.
• c)Rapid break down of acetylcholine exhibits some important functional significance.
• d)It stops the repeated excitation of the muscle fiber and permits the muscle to relax.
• Reuptake Process
• Reuptake is a process in neuromuscular junction, by which the broken down product of neurotransmitter reenters the
presynaptic axon terminal where it is reused.
• Acetylcholinesterase breaks down acetylcholine into inactive choline and acetate.
• Choline is taken back into axon terminal from synaptic cleft because of reuptake
• process.
• There, it is reused in synaptic vesicle to form new acetylcholine molecule.
•

11. • NEUROMUSCULAR BLOCKERS
• Neuromuscular blockers are the drugs, which stop transmission of impulses from nerve fiber to the
muscle fiber via the neuromuscular junctions.
• These drugs are used widely particularly during surgery and trauma care.
• Neuromuscular blockers used during anesthesia relax the skeletal muscles and initiate paralysis
so that surgery can be conducted with less complication.
• Following are important neuromuscular blockers, which are commonly used in clinics and research.
•

12. • 1. Curare
• a)Curare stops the neuromuscular transmission by binding with acetylcholine receptors.
• b)So, the acetylcholine cannot combine with the receptors.
• c)And, the endplate potential cannot develop.
• d)Since curare blocks the neuromuscular transmission by acting on the acetylcholine receptors, it is
also otherwise known as receptor blocker.
• 2. Bungarotoxin
• Bungarotoxin is a toxin from the venom of deadly snakes. It influences the neuromuscular
transmission by blocking the acetylcholine receptors.
•
• Significance of Endplate Potential
• Endplate potential is non-propagative. But it leads to the development of action potential in the
muscle fiber.

13. • DEVELOPMENT OF MINIATURE ENDPLATE POTENTIAL
• a)Miniature endplate potential is a weak endplate potential in neuromuscular junction that is
advanced by the release of a small quantity of acetylcholine from axon terminal.
• b) And, each quantum of this neurotransmitter produces a weak miniature endplate potential. The
amplitude of this potential is only up to 0.5 mV.
• 3. Succinylcholine and Carbamylcholine
• a)These drugs stop the neuromuscular transmission by acting like acetylcholine and keeping the
muscle in a depolarized state.
• b)But, these drugs are not broken down by cholinesterase. So, the muscle remains in a depolarized
state for a long time.
• 4. Botulinum Toxin
• Botulinum toxin is derived from the bacteria Clostridium botulinum. It stops release of acetylcholine
from axon terminal into the neuromuscular junction.

14. • DRUGS ACTIVATING NEUROMUSCULAR JUNCTION
• Neuromuscular junction can be activated because of some drugs such as neostigmine,
physostigmine and diisopropyl fluorophosphate.
• These drugs inactivate the enzyme, acetyl cholinesterase.
• So, the acetylcholine is not hydrolyzed. It results in repeated activation and continuous contraction of
the muscle.
• MOTOR UNIT
• DEFINITION
• Single motor neuron, its axon terminals and the muscle fibers innervated by it are together termed as
motor unit.
• Each motor neuron stimulates a group of muscle fibers through the axon terminals.
• 3) Activation of a motor neuron leads to contraction of all the muscle fibers
• innervated by that neuron.

15. • NUMBER OF MUSCLE FIBERS IN MOTOR UNIT
• Number of muscle fiber in each motor unit varies.
• The motor units of the muscles associated with fine, graded and precise movements exhibit smaller number of muscle
fibers.
•
• For example,
• Laryngeal muscles : 2 to 3 muscle fibers per motor unit
•
• Pharyngeal muscles : 2 to 6 muscle fibers per motor unit
•
• Ocular muscles : 3 to 6 muscle fibers per motor unit
• Muscles associated with crude or coarse movements have motor units with large number of muscle fibers. There are about
120 to 165 muscle fibers in each motor unit in these muscles. Examples are the muscles
• of leg and back.
•

16. • RECRUITMENT OF MOTOR UNITS
• While activating the muscle with weak strength, only a few motor units are involved.
• If the strength of stimulus is enhanced, many motor units are put into action.
• So, the force of contraction enhances. The process by which more and more motor units are put
into action is termed as recruitment of motor unit.
• Thus, the graded response in the muscle is directly proportional to the number of motor units
stimulated.
• 5)Activation of motor units can be studied by electromyography.
•

17. • APPLIED PHYSIOLOGY –
• DISORDERS OF NEUROMUSCULARJUNCTION
• MYASTHENIA GRAVIS
• Myasthenia gravis is an autoimmune disorder of neuromuscular junction happened by antibodies to
cholinergic receptors.
• EATON-LAMBERT SYNDROME
• Eaton-Lambert syndrome is also an autoimmune disorder of neuromuscular junction. It is happened
by antibodies to calcium channels in axon terminal.

18. Fig 1. Drawing of Neuro Muscular Junction ( NMJ )

19. Fig 2. NMJ Architecture

20. Fig. 3. NMJ - Image and Photo

21. Fig 4. Diagram of NMJ

22. Fig 5. Motor Neuron - Structure

23. Fig 6. NMJ - Gros Structure

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