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For neuromuscular transmission there are 3
essential components :

   MOTOR UNITS
   SYNAPTIC CLEFT
   MUSCLE (END PLATE)
The nerve fibre plus the
muscle fibre/ fibres
it innervate form the
motor unit.
 The more delicate the movements, the
 fewer muscle fibres per motor neuron.
 More intense contraction = more motor unit
  & long muscle fibres
 All types of muscle fibre shows all-or-none
 law
 Schwann cell encircles the motor unit
 The neuromuscular junction is separated
  from the extra cellular fluid by extension of
  the terminal Schwann cells and insulates the
  entire structure.
 Contents of the presynatic end:
    - Calcium  channel (P type- fast)
    - Acetylcholine vesicles
    - Active zones
    - Proteins: Synaptotagmin,Synaptobrevin,
      Synaptosome associated protein(SNAP)
    - Presynaptic nAchRs
 3 lacs in an end plate
 45 nm : bound by lipid bilayer memb.
 Active zones
 10,000 mol of Ach in 1 vesicle, loaded by
  Mg++ dependent proton pumping ATPase
 1% – Releasable store
  80% - Reserve pool
  Rest - Stationary pool
   Synthesized in the cell body and by axonal
    transport it reaches the NMJ end of the
    motor neuron.

   ATP + Acetate + CoE- A= Acetyl CoE- A

   Choline + Acetyl CoE- A
             ↓choline acetyltransferase
    Acetylcholine + CoE- A

   Ach: 20%= In free state within axoplasm(VP1)
         80%= Vesicles (VP2)
   Primary Syn.Cleft
    Gap of 20-50µm

   Secondary Syn.
    Cleft

Contents:
- Collagen tissue
 (BM)
Acetylcholinesterase
 nAchRs


 Na Channels
 - Voltage dependent gate (VDG)
 - Timed dependent gate (TDG)

 VDG opens till depol persists but TDG closes
 and cuts off the flow of sodium. TDG does not
 open again until VDG closes and reopens with a
 fresh depol.
Depol of N. terminal


 Opening of Ca channel


        Entry of Ca


Mobilizes membrane bound
           Vesicle


Binding to docking protein


     Fusion of vesicles


Release of ACh into S. Cleft
   The SNARE (soluble N-ethylmaleimide–
    sensitive attachment protein receptors)
    proteins are involved in fusion, docking, and
    release of acetylcholine at the active zone

 Synaptophysin is a glycoprotein component
  of the vesicle membrane.
 Phosphorylation of another membrane
  protein, synapsin, facilitates vesicular
  trafficking to the release site.
   Synaptotagmin is the protein on the vesicular
    membrane acts as a calcium sensor and localizes
    the synaptic vesicles to synaptic zones rich in
    calcium channels, stabilizing the vesicles in the
    docked state.


   Synaptobrevin is a vesicle associated membrane
    protein (VAMP). During depol & entry of Ca
     it unfolds & forms a ternary complex with
    syntaxin/ SNAP-25
   Spontaneous depolarizing potentials at
    neuromuscular junctions can be seen. These
    potentials have only one hundredth the
    amplitude of the evoked end-plate potential
    produced when the motor nerve is stimulated.
    These small-amplitude potentials are called
    miniature end-plate potentials (MEPPs)
 Because MEPPs are too big to be produced by a

  single molecule of acetylcholine, it was deduced
  that they are produced by uniformly sized
  packages, or quanta, of transmitter released from
  the nerve (in the absence of stimulation). The
  stimulus-evoked end-plate potential is the additive
  depolarization produced by the synchronous
  discharge of quanta from several hundred vesicles
   The amount of Ach released by each nerve
    impulse is large, atleast 200 quanta of about
    50,000 molecules each & the number of AchRs

    activated by transmitter released is about
    500,000
DEPOLARIZING
AGENTS
NON-
DEPOLARIZING/
COMPETITIVE
AGENTS
Neuromuscular junction and its physiology

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Neuromuscular junction and its physiology

  • 1.
  • 2.
  • 3. For neuromuscular transmission there are 3 essential components :  MOTOR UNITS  SYNAPTIC CLEFT  MUSCLE (END PLATE)
  • 4. The nerve fibre plus the muscle fibre/ fibres it innervate form the motor unit.
  • 5.  The more delicate the movements, the fewer muscle fibres per motor neuron.  More intense contraction = more motor unit & long muscle fibres  All types of muscle fibre shows all-or-none law  Schwann cell encircles the motor unit
  • 6.  The neuromuscular junction is separated from the extra cellular fluid by extension of the terminal Schwann cells and insulates the entire structure.  Contents of the presynatic end: - Calcium channel (P type- fast) - Acetylcholine vesicles - Active zones - Proteins: Synaptotagmin,Synaptobrevin, Synaptosome associated protein(SNAP) - Presynaptic nAchRs
  • 7.  3 lacs in an end plate  45 nm : bound by lipid bilayer memb.  Active zones  10,000 mol of Ach in 1 vesicle, loaded by Mg++ dependent proton pumping ATPase  1% – Releasable store 80% - Reserve pool Rest - Stationary pool
  • 8. Synthesized in the cell body and by axonal transport it reaches the NMJ end of the motor neuron.  ATP + Acetate + CoE- A= Acetyl CoE- A  Choline + Acetyl CoE- A ↓choline acetyltransferase Acetylcholine + CoE- A  Ach: 20%= In free state within axoplasm(VP1) 80%= Vesicles (VP2)
  • 9. Primary Syn.Cleft Gap of 20-50µm  Secondary Syn. Cleft Contents: - Collagen tissue (BM) Acetylcholinesterase
  • 10.  nAchRs  Na Channels - Voltage dependent gate (VDG) - Timed dependent gate (TDG) VDG opens till depol persists but TDG closes and cuts off the flow of sodium. TDG does not open again until VDG closes and reopens with a fresh depol.
  • 11.
  • 12.
  • 13.
  • 14. Depol of N. terminal Opening of Ca channel Entry of Ca Mobilizes membrane bound Vesicle Binding to docking protein Fusion of vesicles Release of ACh into S. Cleft
  • 15.
  • 16. The SNARE (soluble N-ethylmaleimide– sensitive attachment protein receptors) proteins are involved in fusion, docking, and release of acetylcholine at the active zone  Synaptophysin is a glycoprotein component of the vesicle membrane.  Phosphorylation of another membrane protein, synapsin, facilitates vesicular trafficking to the release site.
  • 17. Synaptotagmin is the protein on the vesicular membrane acts as a calcium sensor and localizes the synaptic vesicles to synaptic zones rich in calcium channels, stabilizing the vesicles in the docked state.  Synaptobrevin is a vesicle associated membrane protein (VAMP). During depol & entry of Ca it unfolds & forms a ternary complex with syntaxin/ SNAP-25
  • 18.
  • 19.
  • 20. Spontaneous depolarizing potentials at neuromuscular junctions can be seen. These potentials have only one hundredth the amplitude of the evoked end-plate potential produced when the motor nerve is stimulated. These small-amplitude potentials are called miniature end-plate potentials (MEPPs)
  • 21.  Because MEPPs are too big to be produced by a single molecule of acetylcholine, it was deduced that they are produced by uniformly sized packages, or quanta, of transmitter released from the nerve (in the absence of stimulation). The stimulus-evoked end-plate potential is the additive depolarization produced by the synchronous discharge of quanta from several hundred vesicles
  • 22. The amount of Ach released by each nerve impulse is large, atleast 200 quanta of about 50,000 molecules each & the number of AchRs activated by transmitter released is about 500,000
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