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