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Neuromuscular Junction: Dr. Niranjan Murthy H L

1. The neuromuscular junction (NMJ) is the synapse between a motor neuron and a muscle fiber, where acetylcholine (Ach) is released from the neuron and binds to nicotinic receptors on the muscle fiber membrane. 2. At the NMJ, Ach is synthesized in the motor neuron, stored in vesicles, and released into the synaptic cleft upon an action potential. Ach then binds nicotinic receptors on the muscle fiber, opening ion channels and generating an endplate potential. 3. Diseases like myasthenia gravis and Lambert-Eaton syndrome affect the NMJ by producing antibodies that reduce Ach receptor numbers or Ach release, respectively, causing muscle weakness

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100% found this document useful (3 votes)
3K views18 pages

Neuromuscular Junction: Dr. Niranjan Murthy H L

1. The neuromuscular junction (NMJ) is the synapse between a motor neuron and a muscle fiber, where acetylcholine (Ach) is released from the neuron and binds to nicotinic receptors on the muscle fiber membrane. 2. At the NMJ, Ach is synthesized in the motor neuron, stored in vesicles, and released into the synaptic cleft upon an action potential. Ach then binds nicotinic receptors on the muscle fiber, opening ion channels and generating an endplate potential. 3. Diseases like myasthenia gravis and Lambert-Eaton syndrome affect the NMJ by producing antibodies that reduce Ach receptor numbers or Ach release, respectively, causing muscle weakness

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nirilib
Copyright
© Attribution Non-Commercial (BY-NC)
We take content rights seriously. If you suspect this is your content, claim it here.
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Download as PPT, PDF, TXT or read online on Scribd
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NEUROMUSCULAR JUNCTION

Dr. Niranjan Murthy H L


Asst. Prof., Dept. of Physiology
Sree Siddhartha Medical College & Hospital, Tumkur
NEUROMUSCULAR
JUNCTION
PHYSIOLOGIC ANATOMY
MECHANISM OF NEUROTRANSMITTER
RELEASE
SIGNAL TRANSDUCTION AT POST-SYNAPTIC
MEMBRANE
ELECTRICAL EVENTS AT MOTOR ENDPLATE
DRUGS ACTING ON NMJ
MYASTHENIA GRAVIS AND LAMBERT- EATON
SYNDROME
NMJ IN CARDIAC AND SMOOTH MUSCLES
NEUROMUSCULAR JUNCTION- STRUCTURE
STRUCTURE OF NMJ
• Alpha Motor neuron- myelinated
• End feet or terminal buttons- loses myelin
sheath
• Synaptic cleft- 50 to 100nm wide
• Post-synaptic gutter
• Sub-synaptic clefts- increases surface area
• Acetylcholine receptors- 15 to 40 million
• MOTOR END-PLATE
SYNTHESIS AND STORAGE OF
Ach
• Choline+Acetyl Co-A+ATP
Choline acyltransferase
Acetyl-choline
cholinesterase
Choline + Acetate
RELEASE OF Ach
• Action potential at end-feet
• Opening of voltage-gated Ca2+
channels
• Exocytosis of Ach- 60 vesicles with
10,000 molecules each are released
SIGNAL TRANSDUCTION
•Ach-gated ion channels
has 5 subunits: 2α,1β,1γ and

•2 Ach molecules binds to
2α subunits
•Opening of the channel to
cations
•Influx of Na+ ions
•End-plate potential
ELECTRICAL EVENTS
• RMP of muscle membrane is –90mv
• Na+ influx raises the end-plate potential
(EPP) by 50-75mv
• Opening of voltage-gated Na+ channels
• Propogated action potential
• MINIATURE END-PLATE POTENTIAL
DRUGS ACTING ON NMJ
• DRUGS THAT INCREASE ACTIVITY
OF NMJ
• Drugs with Ach-like action
Eg: Nicotine, Methacholine & Carbachol
• Drugs that inactivate acetylcholinesterases
Eg: Physostigmine, Neostigmine,
Diisopropyl fluorophosphate
• DRUGS THAT BLOCK NMJ
A) By inhibiting Ach release
Eg: Botulinum toxin
B) By antagonizing Ach action
1. By competitive inhibition
Eg: Curariform drugs
2. By persistent depolarisation
Eg: Succinylcholine
MYASTHENIA GRAVIS
MYASTHENIA GRAVIS
• auto-immune disorder
• Antibodies against Ach-gated channels
• Causes endocytosis of receptors
• C/f: muscle weakness, ptosis, respiratory
failure
• Rx- Anticholinesterases like neostigmine,
physostigmine
LAMBERT-EATON
SYNDROME
• Antibodies against
Voltage-gated Ca2+
channels at end-feet
• Reduced Ach release
• Muscle strength
increases with
prolonged
contractions
NMJ IN SMOOTH AND
CARDIAC MUSCLES
• Cholinergic as well as noradrenergic fibers
• Varicosities- enlargements devoid of schwann
cells and containing vesicles
• Noradrenergic neurons have upto 20,000
varicosities per neuron each 5μm apart
• One neuron innervate many effector cells
• Diffuse junctions and contact junctions
• Synapse en passant
• Neurotransmitters- Ach, Noradrenaline,etc
• Excitatory or inhibitory junctional potentials-
depends on the type of receptor
NEUROMUSCULAR JUNCTION

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