Structure of the neuromuscular junction and events occurring at the neuromuscular junction.

1. GOOD
AFTERNOON
EVERYONE!

2. Facilitator: Shailesh Adhikari
Presented by group “C”
• Bhawana Kafle
• Bibek Bhandari
• Bijaya Pun
• Chandan Kumar Sah
• Deekshya Devkota
• Dilip Kumar Thakur
• Duman Thapa
• Gyanendra Bakhati
• Gyanendra Suyal
• Sujan Tamang

4. Learning objective
-structure of neuromuscular junction
-series of events occurring at neuromuscular junction

5. WHAT IS
NEUROMUSCULAR
JUNCTION?
It is the junction
between terminal
of motor neuron
and muscle fiber.

6. Structures of axon terminal:
• Presynaptic membrane
• Mitochondria
• Synaptic vesicles
• Sodium choline co-transporter
• Microfilaments and tubules
• Voltage gated calcium channels

7. Structures of synaptic
cleft:
- basal lamina (organized layer
of extracellular matrix inside the
synaptic cleft)
-Acetyl cholinesterase enzyme
This Photo by Unknown Author is licensed under CC BY-SA-NC

8. Structures of postsynaptic membrane:
• Synaptic trough or gutter
- motor endplate invaginates inside the
muscle fiber and form depression
• subneural cleft: numerous folds of post
synaptic membrane
-nicotinic acetylcholine receptors
- ligand gated ion channels

9. • Neuromuscular
transmission
Transfer of information
from motor nerve
endings to the muscle
fiber through
neuromuscular junction
to initiate muscle
contraction.

10. Events in neuromuscular transmission:
1. Propagation of action potential to the axon terminal
2.Opening of voltage gated calcium channels in the membrane
of axon terminal
• Influx of calcium ions from ECF to the axon terminal
• Migration and attachment of acetylcholine vesicles to the presynaptic
membrane
3.Release of acetylcholine via exocytosis
• Acetylcholine diffuses into synaptic cleft

11. 4. Action of acetylcholine
• binds with nicotinic Ach receptor in
the post synaptic membrane
• Formation of Ach receptor complex
• opening ligand gated sodium
channels
• Sodium from ECF diffuses into muscle
fiber
• End plate potential develops

12. 5. Development of end plate potential(EPP)
• RMP at muscle fiber is -90mv
• Sudden influx of Na+ into the muscle fiber when the Ach gated ion channels
open causes electrical potential inside the fiber at the local area of the end plate
to increase in the positive direction as much as 50 to 75mv creating a local
potential called endplate potential.
• EPP is a graded potential(non-propagative, short distance signal)
• EPP initiates an action potential that spreads along the muscle
membrane and thus causes muscle contraction.

13. 5. Destruction of acetylcholine
• Rapidly removed by two means:
1) destroyed by enzyme acetylcholinesterase
2)small amount of acetylcholine(Ach) diffuses out of synaptic space
• Ach in synaptic cleft is destroyed very quickly, within 1millisec by
enzyme Ach esterase.
• Ach is so potent that even this short duration is sufficient to excite the
muscle fiber.
• Rapid destruction of acetylcholine prevents the repeated excitation of
muscle fiber and allows muscles to relax.

14. Reuptake process
-Ach esterase splits Ach into inactive choline and acetate.
Acetylcholine Ach esterase acetate+ choline
-Choline is taken back into axon terminal from synaptic cleft by nerve
ending via sodium choline co-transport and reused for synthesis of
acetylcholine
-acetate diffuses into ECF
choline + acetate ATP acetylcholine

15. Miniature end plate potential
• Small quanta of Ach released at resting condition which in turn
generate small potential difference
• about 0.5mv
• When a nerve impulse reaches the ending the number of quanta
released by several order of magnitude that result in large endplate
potential that exceeds the firing level of muscle fiber .

16. Neuromuscular blockers
• Drugs which prevent transmission of impulse
across neuromuscular junction by blocking Ach
receptors.
• Eg: curare , bungarotoxin(from snake
venom),botulinum toxin
• Useful in surgical and trauma care to restrict
muscle contraction.

17. Neuromuscular stimulators
• Drugs stimulating neuromuscular transmission
• Mechanism:
1. Inactivates Ach esterase
2. Repeated stimulation from acetylcholine
3. Continuous contraction of muscle fiber
use: treating weak or paralyzed muscle
Example : Neostigmine, Physostigmine

18. • Applied physiology
Myasthenia gravis
1. Autoantibodies against acetylcholine
receptors.
2. Blockade of acetylcholine receptors.

19. References:
• GUYTON AND HALL : Textbook of Medical Physiology(13th edition
pg.89)
• GANONG’S Review of Medical Physiology(23rd edition 2010, page
number:115)
• K Sembulingam : Essentials of MEDICAL PHYSIOLOGY(6th edition 2013,
page number:200)
• https://www.khanacademy.org/
• https://www.ncbi.nlm.nih.gov/
• https://www.wikipedia.org/

20. Presented by
• Bhawana Kafle
• Bibek Bhandari
• Bijaya Pun
• Chandan Kumar Sah
• Deekshya Devkota
• Dilip Kumar Thakur
• Duman Thapa
• Gyanendra Bakhati
• Gyanendra Suyal
• Sujan Tamang Thank you!