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FOUNDATION MODULE
SMALL GROUP DISCUSSION
First year MBBS Batch- 50 (2023)_
Dr. Ali Zain
Batch
Date:-16th March2023
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Neuromuscular
junction and
Neuromuscular
Transmission
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Motto Vision; The Dream/Tomorrow
• To impart evidence based
research oriented medical
education
• To provide best possible
patient care
• To inculcate the values of
mutual respect and ethical
practice of medicine
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LEARNING OBJECTIVES
• structure of neuromuscular junction
• series of events occurring at neuromuscular junction
• Myasthenia Gravis
• Lambert Eaton syndrome
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WHAT IS NEUROMUSCULAR JUNCTION?
• It is the junction
between terminal
of motor neuron and
muscle fiber.
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1. Structures of axon terminal
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• Presynaptic membrane
• Mitochondria
• Synaptic vesicles
• Sodium choline
co-transporter
• Microfilaments and tubules
• Voltage gated calcium
channels
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Reference : Guyton and hall textbook of
medical physiology, 8
• Basal lamina (organized layer
of extracellular matrix inside
the synaptic cleft)
- Acetyl cholinesterase enzyme
2. Structures of synaptic cleft:
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3. 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
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4. Neuromuscular transmission
Transfer of information from motor nerve endings to
the muscle fiber through neuromuscular junction to
initiate muscle contraction
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
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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
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13. 5. Development of end plate potential
• 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.
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6. 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.
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7. 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
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8. 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 .
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• Applied physiology
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i) Myasthenia
gravis
1. Autoantibodies against
acetylcholine receptors.
2. Blockade of acetylcholine
receptors.
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ii) Lambert Eaton Syndrome
Disorder of neuromuscular junction in
which in which autoantibodies are made
against the presynaptic Voltage gated
calcium channels.
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ASSESSMENT
Question:
A 35-year-old woman presents with weakness and fatigue in
her upper extremities. On examination, there is a noticeable
decrease in her grip strength, and she has difficulty raising
her arms above her head. She reports no sensory changes or
pain. Further testing reveals abnormalities in her NMJ
transmission.
• What is the neuromuscular junction (NMJ)?
• How does NMJ transmission occur?
• What are some common causes of disturbances
in NMJ transmission?
• What diagnostic tests can be used to assess NMJ
transmission?
• What are the clinical manifestations of NMJ
transmission disorders?
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References
• Guyton and Hall Textbook Of Medical
Physiology fourteenth edition
• Ganong’s Review of Medical Physiology
• Google and wikipedia for images for concepts
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Suggested research article
https://www.ncbi.nlm.nih.gov/books/NBK470413/
• Physiology, Neuromuscular Junction
Abdillahi Omar; Komal Marwaha; Pradeep C. Bollu.
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• Steps to Access HEC Digital Library
1. Go to the website of HEC National Digital Library.
2. On Home Page, click on the INSTITUTES.
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Private Sector and other Institutes which have access to HEC
National Digital Library HNDL.
4. Select your desired Institute.
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7. You can find a Journal by clicking on JOURNALS AND DATABASE
and enter a keyword to search for your desired journal
Link:https://www.topstudyworld.com/2020/05/access-hec-
digital-library.html?m=1
How To Access Digital Library
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HOW TO APPLY FOR HEC DIGITAL
LIBRARY IF YOU ARE NOT MEMBER
• If you are not a member of HEC national
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