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Neuromuscular junction
Neuromuscular junction
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  1. 1. NEUROMUSCULAR JUNCTION Submitted by: Preeti Reddy Komal Pahal Binal Ramani Submitted to: Praveen Gupta Sir 1
  2. 2. NEUROMUSCULAR JUNCTION A neuromuscular junction (or myoneural junction) is a chemical synapse formed by the contact between a motor neuron and a muscle fibre. It is at the neuromuscular junction that a motor neuron is able to transmit a signal to the muscle fibre causing muscle contraction. Source-Google 2
  3. 3. 3 MOTOR NEURON AND FROM WHERE IT ORIGINATES Source-Google A motor neuron is a neuron whose cell body is located in the motor cortex, brainstem or the spinal cord and whose axon projects to the spinal cord or outside of the spinal cord to directly or indirectly control effector organs mainly muscles and glands.
  4. 4. 4Source-Google
  5. 5. 5 Stimulus-response pathway (Source- Google)
  6. 6. 6 ANATOMY OF NMJ MOTOR END PLATE  The nerve fiber forms a complex of branching nerve terminals that invaginate into the surface of the muscle fiber but lie outside the muscle fiber plasma membrane  Entire structure - motor endplate.  Covered by one or more Schwann cells that insulate it from the surrounding fluids. Source-Google
  7. 7. 7 Synaptic trough: invagination in the motor endplate membrane Synaptic clefts: 20-30nm wide Contains large quantities of acetylcholinesterase (AchE) Source-Guyton & Hall
  8. 8. 8 Subneural clefts: Increase the surface area of the post-synaptic membrane  Ach gated channels at tops Voltage gated Na+ channel in bottom half Source-Guyton &Hall
  9. 9. 9 AXON TERMINAL  SYNAPTIC VESICLES – Size 40 nanometers – Formed by the Golgi apparatus in the cell body of the motor neuron in the spinal cord. – Transported by axoplasm to the neuromuscular junction at the tips of the peripheral nerve fibers. – About 300,000 of these small vesicles collect in the nerve terminals of a single skeletal muscle end plate. Source-Guyton &Hall
  10. 10. 10 MITOCHONDRIA Numerous Supply ATP Energy source for synthesis of excitatory neurotransmitter, acetylcholine Source- Guyton & Hall
  11. 11. 11 Secretion Of Acetylcholine By The Nerve Terminals Nerve impulses reaches at the neuromuscular junction. No. of released synaptic vesicles of acetylcholine are about 125 released from the terminals into the synaptic space . NEURAL MEMBRANE • On inside of neural membrane linear dense bars • To each side of dense bars, protein particles are present • Voltage gated calcium channels • Action potential Source-Guyton & Hall
  12. 12. 12 Voltage-gated calcium channels 1.When action potential spreads over the terminal leads to opening of the channels. 2.Allows calcium ions to diffuse from the synaptic space to the interior of the nerve terminal. 3.Entry of calcium ions is an effective stimulus for causing the acetylcholine release from the vesicles is then emptied through the neural membrane adjacent to the dense bars.
  13. 13. 13 Action potentialAction potential Ca2+Ca2+ Presynaptic terminal Presynaptic terminal Voltage-gated Ca2+ channel Voltage-gated Ca2+ channel Action potentials arriving at the presynaptic terminal cause voltage-gated Ca2+ channels to open. Source- Google
  14. 14. 14 PRESYNAPTIC NERVE TERMINAL OR NERVE TERMINAL  Channels opening  Permission of calcium ions for diffusion  From synaptic space of interior of terminal  Calcium ions exert influence on acetylcholine vesicles  Carrying and pushing them towards neural membrane  Fuse with neural membrane  Exocytosis
  15. 15. 15 Ca2+ diffuse into the cell and cause synaptic vesicles to release acetylcholine, a neurotransmitter molecule. Ca2+Ca2+ Synaptic vesicle Synaptic vesicle AcetylcholineAcetylcholine Ca2+ uptake into the terminal causes release of the neurotransmitter acetylcholine into synaptic cleft , which has been synthesized and stored into synaptic vesicles Source- Google
  16. 16. 16 Effect of acetylcholine on postsynaptic muscle fibre Sub-neural cleft  Acetylcholine receptors  Acetylcholine gated ion channels  Location is at the mouth of sub-neural cleft  Lying immediately below the dense bars  Lying side by side in a circle  Tubular channels Source-Guyton &Hall
  17. 17. 17 Acetylcholine diffuses from the presynaptic terminal across the synaptic cleft. Synaptic cleftSynaptic cleft AcetylcholineAcetylcholine Presynaptic terminal Presynaptic terminal Ca2+Ca2+ • Ach travels across the synaptic cleft to postsynaptic membrane which is also known as motor end plate. Source- Google
  18. 18. 18 Acetylcholine bound to receptor site opens ligand-gated Na+ channel Acetylcholine bound to receptor site opens ligand-gated Na+ channel Ca2+Ca2+ Voltage-gated Ca2+ channel Voltage-gated Ca2+ channel Synaptic vesicle Synaptic vesicle Postsynaptic membrane Postsynaptic membrane AcetylcholineAcetylcholine 4 Synaptic cleftSynaptic cleft Action potentialAction potential Presynaptic terminal Presynaptic terminal Na+Na+ 1 2 3 1 2 3 1 2 3 11 2 3 4 Source- Google
  19. 19. 19 Acetylcholine molecules combine with their receptor sites and cause ligand-gated Na+ channels to open. Na+Na+ Acetylcholine bound to receptor site opens ligand-gated Na+ channel Acetylcholine bound to receptor site opens ligand-gated Na+ channel Source- Google
  20. 20. 20 ACETYLCHOLINE RECEPTOR A protein complex Molecular weight-275,000 Two alpha and one each beta, delta and gamma proteins. Channel remains constricted until two acetylcholine molecules attach respectively to the two alpha subunit proteins. Causes a conformational change that opens the channel. Source-Google
  21. 21. 21 Source-Guyton & Hall OPENING OF CHANNEL  Conformational change  Opening of channels  Opened acetylcholine channel has diameter 0.65nanometer  Permission to ions  Na, K and Ca  Negative ions cannot move such as Cl
  22. 22. 22 Source-Google
  23. 23. 23  Strong negative charges in the mouth of channel  Repel the negative ions OPENING OF CHANNEL WHY Na IONS RUSH INSIDE  Large amount of Na ions rush inside  Two positive ions in large concentration  Sodium and potassium ion  Sodium ion in extracellular fluid  Potassium ion in intracellular fluid
  24. 24. 24 Negative potential inside the membrane  -80 to -90 mv Pulls the positively charged sodium ions inside the fibre. Prevention of efflux of potassium ions when they attempt to pass outward. Source-Guyton & Hall
  25. 25. 25 END PLATE POTENTIAL Opening the acetylcholine-gated channels allows large numbers of sodium ions to pour to the inside of the fiber  Sodium ions carry with them large numbers of positive charges  Creates a local positive potential change inside the muscle fiber membrane, called the end plate potential. End plate potential initiates an action potential that spreads along the muscle membrane Causes muscle contraction
  26. 26. 26 Acetyl cholinesterase ends Ach activity at N.M junction • To ensure purposeful movement ,muscle cell electrical response is turned off by acetylcholinestrase(AchE), which degrade Ach to choline & acetate • About 50%of choline is returned to the presynaptic terminal by Na+choline transport to be reused for Ach synthesis. • Now muscle fiber can relax ,if sustained contraction is needed for the desired movement another motor neuron AP leads to release of more Ach
  27. 27. 27
  28. 28. 28 Source-Google
  29. 29. 29 Synthesis and destruction of acetylcholine (Source-Google)
  30. 30. 30 Excitation–Contraction Coupling A motor neuron connects to a muscle at the neuromuscular junction, where a synaptic terminal forms a synaptic cleft with a motor-end plate. The neurotransmitter acetylcholine diffuses across the synaptic cleft, causing the depolarization of the sarcolemma. The depolarization of the sarcolemma stimulates the sarcoplasmic reticulum to release Ca2+, which causes the muscle to contract.
  31. 31. 31 Source-Google
  32. 32. 32 Reference: Guyton & Hall Textbook Of Medical Physiology
  33. 33. 33