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
1ε
•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