Neuromuscular junction and its physiology


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Neuromuscular junction and its physiology

  1. 1. For neuromuscular transmission there are 3essential components : MOTOR UNITS SYNAPTIC CLEFT MUSCLE (END PLATE)
  2. 2. The nerve fibre plus themuscle fibre/ fibresit innervate form themotor unit.
  3. 3.  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
  4. 4.  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
  5. 5.  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
  6. 6.  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)
  7. 7.  Primary Syn.Cleft Gap of 20-50µm Secondary Syn. CleftContents:- Collagen tissue (BM)Acetylcholinesterase
  8. 8.  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.
  9. 9. Depol of N. terminal Opening of Ca channel Entry of CaMobilizes membrane bound VesicleBinding to docking protein Fusion of vesiclesRelease of ACh into S. Cleft
  10. 10.  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.
  11. 11.  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
  12. 12.  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)
  13. 13.  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
  14. 14.  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