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Synapse and NMJ Dr Irum Rehman
DEFINITION <ul><li>“  The site of connection of motor neuron with skeletal muscle making a functional contact is called as...
Neuromuscular Junction <ul><li>Neuromuscular Junction </li></ul><ul><li>A neuromuscular junction exists between a motor ne...
 
INNERVATION OF SKELETAL MUSCLE FIBERS <ul><li>Large,  myelinated  nerve fibers </li></ul><ul><li>Originate from  large mot...
 
 
MOTOR END PLATE <ul><li>The nerve fiber forms  a complex of  branching nerve terminals that invaginate into the surface of...
 
AXON TERMINAL <ul><li>SYNAPTIC VESICLES  </li></ul><ul><ul><li>S ize  40 nanometers  </li></ul></ul><ul><ul><li>Formed by ...
 
<ul><li>MITOCHONDRIA  </li></ul><ul><ul><li>Numerous </li></ul></ul><ul><ul><li>Supply  ATP  </li></ul></ul><ul><ul><li>En...
 
<ul><li>VOL TAGE GATED CALCIUM CHANNELS  </li></ul><ul><ul><li>Protein particles  that penetrate the neural membrane on ea...
<ul><ul><li>The vesicles then fuse with the neural membrane and  empty their acetylcholine into the synaptic space by the ...
 
MUSCLE FIBER MEMBRANE <ul><li>SYNAPTIC TROUGH  </li></ul><ul><ul><li>The muscle fiber membrane where it is  invaginated by...
 
<ul><li>SUBNEURAL CLEFT  </li></ul><ul><ul><li>Numerous  smaller  folds of the muscle membrane   at the bottom of the gutt...
 
ACETYLCHOLINE RECEPTORS <ul><li>Acetylcholine-gated ion channels </li></ul><ul><li>Molecular weight -275,000 </li></ul>
 
<ul><li>SUBUNITS  </li></ul><ul><ul><li>Two  alpha, one  each of  beta, delta, and gamma  </li></ul></ul><ul><ul><li>Penet...
 
 
 
<ul><li>OPENED Ach CHANNEL  </li></ul><ul><ul><li>2 Ach molecules attached to the alpha subunit of receptor  </li></ul></u...
 
<ul><li>SODIUM IONS </li></ul><ul><ul><li>Far more sodium ions flow through the acetylcholine channels to the inside than ...
<ul><li>END PLATE POTENTIAL  </li></ul><ul><ul><li>Opening the acetylcholine-gated channels allows large numbers of sodium...
 
Events of Neuromuscular Junction <ul><li>Propagation of an action potential to a terminal button of motor neuron. </li></u...
 
Examples of Chemical Agents and Diseases that Affect the Neuromuscular Junction <ul><li>Mechanism  that   Chemicals or Dis...
Synapse  <ul><li>Definition  </li></ul><ul><li>Types </li></ul><ul><li>Anatomical and Physiological </li></ul>
Properties/ Characteristics <ul><li>A combination of neurotransmitter and a synapse will always be either  </li></ul><ul><...
One-way conduction <ul><li>Synapses  generally permit  conduction of impulses in one-way i.e.   </li></ul><ul><ul><li>from...
Spatial Summation in Neurons <ul><li>Excitation of a single presynaptic terminal?? </li></ul><ul><ul><li>0.5 to 1 millivol...
Temporal Summation <ul><li>A presynaptic terminal fire </li></ul><ul><ul><li>changed postsynaptic potential  </li></ul></u...
Facilitation of Neurons <ul><li>If the  summated postsynaptic potential  is excitatory…………. </li></ul><ul><li>But has  not...
 
Fatigue of Synaptic Transmission. <ul><li>When  excitatory synapses  are repetitively stimulated at  a rapid rate </li></u...
Mechanism Of Fatigue <ul><li>Exhaustion or partial exhaustion  of the stores of transmitter substance </li></ul><ul><li>Pr...
Effect of Acidosis or Alkalosis on Synaptic Transmission. <ul><li>Neurons are highly responsive to  changes in  pH </li></...
Effect of Hypoxia <ul><li>Neuronal excitability is also highly dependent on an  adequate supply of oxygen . </li></ul><ul>...
Effect of Drugs <ul><li>Stimulants: </li></ul><ul><li>Caffeine ,  Theophylline , and  Theobromine ,   </li></ul><ul><ul><l...
Synaptic delay Is the minimum time required for transmission across the synapse   the  synaptic delay  0.5 millisecond .  ...
Convergence <ul><li>When many  </li></ul><ul><li>pre-synaptic neurons   </li></ul><ul><li>converge  on  </li></ul><ul><li>...
Divergence <ul><li>Axons of most  </li></ul><ul><li>pre-synaptic neurons  divide into many branches that  diverge </li></u...
Properties of synapse <ul><li>Neurotransmitter receptor complex </li></ul><ul><li>One-way conduction </li></ul><ul><li>Sum...
Comparison of Synapse and NMJ
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Neuromuscular junction and synapses by DR.IRUM

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Neuromuscular junction and synapses by DR.IRUM

  1. 2. Synapse and NMJ Dr Irum Rehman
  2. 3. DEFINITION <ul><li>“ The site of connection of motor neuron with skeletal muscle making a functional contact is called as NEUROMUSCULAR JUNCTION. ” </li></ul>
  3. 4. Neuromuscular Junction <ul><li>Neuromuscular Junction </li></ul><ul><li>A neuromuscular junction exists between a motor neuron and a skeletal muscle. </li></ul><ul><li>- Synapse </li></ul><ul><li>A junction between two excitable tissues. </li></ul>
  4. 6. INNERVATION OF SKELETAL MUSCLE FIBERS <ul><li>Large, myelinated nerve fibers </li></ul><ul><li>Originate from large motor neurons in the anterior horns of the spinal cord </li></ul><ul><li>Each nerve fiber , branches and stimulates from three to several hundred skeletal muscle fibers </li></ul><ul><li>The action potential initiated in the muscle fiber by the nerve signal travels in both directions toward the muscle fiber ends </li></ul>
  5. 9. MOTOR END PLATE <ul><li>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 </li></ul><ul><li>Entire structure - motor endplate. </li></ul><ul><li>Covered by one or more Schwann cells that insulate it from the surrounding fluids. </li></ul>
  6. 11. AXON TERMINAL <ul><li>SYNAPTIC VESICLES </li></ul><ul><ul><li>S ize 40 nanometers </li></ul></ul><ul><ul><li>Formed by the Golgi apparatus in the cell body of the motor neuron in the spinal cord. </li></ul></ul><ul><ul><li>Transported by axoplasm to the neuromuscular junction at the tips of the peripheral nerve fibers. </li></ul></ul><ul><ul><li>About 300,000 of these small vesicles collect in the nerve terminals of a single skeletal muscle end plate. </li></ul></ul>
  7. 13. <ul><li>MITOCHONDRIA </li></ul><ul><ul><li>Numerous </li></ul></ul><ul><ul><li>Supply ATP </li></ul></ul><ul><ul><li>Energy source for synthesis of excitatory neurotransmitter, acetylcholine </li></ul></ul><ul><li>DENSE BARS </li></ul><ul><ul><li>Present on the inside surface of neural </li></ul></ul><ul><ul><li>membrane </li></ul></ul>
  8. 15. <ul><li>VOL TAGE GATED CALCIUM CHANNELS </li></ul><ul><ul><li>Protein particles that penetrate the neural membrane on each side 0f dense bar </li></ul></ul><ul><ul><li>When an action potential spreads over the terminal, these channels open and calcium ions diffuse to the interior of the nerve terminal. </li></ul></ul><ul><ul><li>The calcium ions, exert an attractive influence on the acetylcholine vesicles, drawing them to the neural membrane adjacent to the dense bars. </li></ul></ul>
  9. 16. <ul><ul><li>The vesicles then fuse with the neural membrane and empty their acetylcholine into the synaptic space by the process of exocytosis </li></ul></ul><ul><ul><li>Calcium acts as an effective stimulus for causing acetylcholine release from the vesicles </li></ul></ul><ul><ul><li>Acetylcholine is then emptied through the neural membrane adjacent to the dense bars and binds with acetylcholine receptors in the muscle fiber membrane </li></ul></ul>
  10. 18. MUSCLE FIBER MEMBRANE <ul><li>SYNAPTIC TROUGH </li></ul><ul><ul><li>The muscle fiber membrane where it is invaginated by a nerve terminal and a depression is formed </li></ul></ul><ul><li>SYNAPTIC CLEFT </li></ul><ul><ul><li>The space between the nerve terminal and the fiber membrane is called the synaptic space or synaptic cleft </li></ul></ul>
  11. 20. <ul><li>SUBNEURAL CLEFT </li></ul><ul><ul><li>Numerous smaller folds of the muscle membrane at the bottom of the gutter </li></ul></ul><ul><ul><li>Greatly increase the surface area. </li></ul></ul><ul><li>ACETYLCHOLINE RECEPTORS </li></ul><ul><ul><li>Acetylcholine-gated ion channels </li></ul></ul><ul><ul><li>Located almost entirely near the mouths of the sub neural clefts lying immediately below the dense bar areas </li></ul></ul>
  12. 22. ACETYLCHOLINE RECEPTORS <ul><li>Acetylcholine-gated ion channels </li></ul><ul><li>Molecular weight -275,000 </li></ul>
  13. 24. <ul><li>SUBUNITS </li></ul><ul><ul><li>Two alpha, one each of beta, delta, and gamma </li></ul></ul><ul><ul><li>Penetrate all the way through the membrane </li></ul></ul><ul><ul><li>Lie side by side in a circle- form a tubular channel </li></ul></ul><ul><ul><li>Two acetylcholine molecules attach to the two alpha subunits, opens the channel </li></ul></ul><ul><li>RESTING STATE </li></ul><ul><ul><li>2 Ach molecules not attached to the alpha subunit </li></ul></ul><ul><ul><li>Channel remains constricted </li></ul></ul>
  14. 28. <ul><li>OPENED Ach CHANNEL </li></ul><ul><ul><li>2 Ach molecules attached to the alpha subunit of receptor </li></ul></ul><ul><ul><li>Diameter - 0.65 nanometer </li></ul></ul><ul><ul><li>Allows important positive ions— SODIUM, potassium, and calcium to move easily through the opening. </li></ul></ul><ul><ul><li>Disallows negative ions, such as chloride to pass through because of strong negative charges in the mouth of the channel that repel these negative ions. </li></ul></ul>
  15. 30. <ul><li>SODIUM IONS </li></ul><ul><ul><li>Far more sodium ions flow through the acetylcholine channels to the inside than any other ions </li></ul></ul><ul><ul><li>The very negative potential on the inside of the muscle membrane, –80 to –90 mili volts, pulls the positively charged sodium ions to the inside of the fiber </li></ul></ul><ul><ul><li>Simultaneously prevents efflux of the positively charged potassium ions when they attempt to pass outward </li></ul></ul>
  16. 31. <ul><li>END PLATE POTENTIAL </li></ul><ul><ul><li>Opening the acetylcholine-gated channels allows large numbers of sodium ions to pour to the inside of the fiber </li></ul></ul><ul><ul><li>Sodium ions carry with them large numbers of positive charges </li></ul></ul><ul><ul><li>Creates a local positive potential change inside the muscle fiber membrane, called the end plate potential. </li></ul></ul><ul><ul><li>End plate potential initiates an action potential that spreads along the muscle membrane </li></ul></ul><ul><ul><li>Causes muscle contraction </li></ul></ul>
  17. 33. Events of Neuromuscular Junction <ul><li>Propagation of an action potential to a terminal button of motor neuron. </li></ul><ul><li>Opening of voltage-gated Ca 2+ channels. </li></ul><ul><li>Entry of Calcium into the terminal button. </li></ul><ul><li>Release of acetylcholine (by exocytosis). </li></ul><ul><li>Diffusion of Ach across the space. </li></ul><ul><li>Binding of Ach to a receptor on motor end plate. </li></ul>
  18. 35. Examples of Chemical Agents and Diseases that Affect the Neuromuscular Junction <ul><li>Mechanism that Chemicals or Disease </li></ul><ul><li>Alters Release of Acetylcholine </li></ul><ul><li>* Cases explosive release of acetylcholine * Black widow spider venom </li></ul><ul><li>* Blocks release of acetylcholine * Clostridium botulinum toxin </li></ul><ul><li>Block acetylcholine Receptor </li></ul><ul><li>* Bind reversibly * Curare </li></ul><ul><li>* Auto antibodies inactivate acetylcholine * Myasthenia gravis </li></ul><ul><li>receptors </li></ul><ul><li>Prevents inactivation of acetylcholine </li></ul><ul><li>* Irreversibly inhibits acetylcholinesterase * Organophosphates </li></ul><ul><li>* Temporary inhibits acetylcholinesterase * Neostigmine </li></ul>
  19. 36. Synapse <ul><li>Definition </li></ul><ul><li>Types </li></ul><ul><li>Anatomical and Physiological </li></ul>
  20. 37. Properties/ Characteristics <ul><li>A combination of neurotransmitter and a synapse will always be either </li></ul><ul><li>Excitatory </li></ul><ul><li>Or </li></ul><ul><li>2 Inhibitory </li></ul>
  21. 38. One-way conduction <ul><li>Synapses generally permit conduction of impulses in one-way i.e. </li></ul><ul><ul><li>from pre-synaptic to </li></ul></ul><ul><ul><li>post-synaptic neuron. </li></ul></ul>
  22. 39. Spatial Summation in Neurons <ul><li>Excitation of a single presynaptic terminal?? </li></ul><ul><ul><li>0.5 to 1 millivolt </li></ul></ul><ul><li>10 to 20 millivolts - required to reach threshold </li></ul><ul><li>Many presynaptic terminals are usually stimulated at the same time. </li></ul><ul><li>Add to one another until neuronal excitation </li></ul><ul><li>Spatial summation </li></ul><ul><ul><li>Summing simultaneous postsynaptic potentials by activating multiple terminals on widely spaced areas of the neuronal membrane </li></ul></ul>
  23. 40. Temporal Summation <ul><li>A presynaptic terminal fire </li></ul><ul><ul><li>changed postsynaptic potential </li></ul></ul><ul><ul><li>lasts up to 15 milliseconds </li></ul></ul><ul><li>Second opening of the same channels -increase the postsynaptic potential to - still greater level </li></ul><ul><li>Successive discharges from a single presynaptic terminal </li></ul><ul><li>Rapid enough- add to one another </li></ul><ul><li>This type of summation is called Temporal summation . </li></ul>
  24. 41. Facilitation of Neurons <ul><li>If the summated postsynaptic potential is excitatory…………. </li></ul><ul><li>But has not risen high enough to reach the threshold </li></ul><ul><li>The neuron is said to be facilitated . </li></ul><ul><li>Another excitatory signal - excite the neuron very easily </li></ul>
  25. 43. Fatigue of Synaptic Transmission. <ul><li>When excitatory synapses are repetitively stimulated at a rapid rate </li></ul><ul><li>Number of discharges by the postsynaptic neuron is at first very great </li></ul><ul><li>But the firing rate becomes progressively less in succeeding milliseconds or seconds . </li></ul><ul><li>Fatigue of synaptic transmission . </li></ul><ul><li>Protective mechanism </li></ul><ul><ul><li>Against excess neuronal activity </li></ul></ul><ul><ul><ul><li>Prevent over excitation </li></ul></ul></ul>
  26. 44. Mechanism Of Fatigue <ul><li>Exhaustion or partial exhaustion of the stores of transmitter substance </li></ul><ul><li>Progressive inactivation of many of the postsynaptic membrane receptors </li></ul><ul><li>Slow development of abnormal conc. of ions inside the postsynaptic neuronal cell </li></ul>
  27. 45. Effect of Acidosis or Alkalosis on Synaptic Transmission. <ul><li>Neurons are highly responsive to changes in pH </li></ul><ul><li>Alkalosis greatly increases neuronal excitability </li></ul><ul><ul><li>8.0 often causes cerebral epileptic seizures </li></ul></ul><ul><li>Acidosis greatly depresses neuronal activity; </li></ul><ul><ul><li>a fall in pH from 7.4 to below 7.0 </li></ul></ul><ul><ul><li>Severe diabetic or uremic acidosis, </li></ul></ul><ul><ul><li>Coma </li></ul></ul>
  28. 46. Effect of Hypoxia <ul><li>Neuronal excitability is also highly dependent on an adequate supply of oxygen . </li></ul><ul><li>Cessation of oxygen for only a few seconds can cause complete inexcitability of some neurons </li></ul><ul><ul><li>If Brain’s blood flow is temporarily interrupted, </li></ul></ul><ul><ul><li>Within 3 to 7 seconds , the person becomes unconscious. </li></ul></ul>
  29. 47. Effect of Drugs <ul><li>Stimulants: </li></ul><ul><li>Caffeine , Theophylline , and Theobromine , </li></ul><ul><ul><li>found in coffee, tea, and cocoa </li></ul></ul><ul><li>By reducing the threshold for excitation of neurons. </li></ul><ul><li>Strychnine inhibits the action of some inhibitory transmitter substances </li></ul><ul><li>Inhibitory </li></ul><ul><li>Most Anesthetics increase the neuronal membrane threshold for excitation </li></ul>
  30. 48. Synaptic delay Is the minimum time required for transmission across the synapse the synaptic delay 0.5 millisecond . <ul><li>This time is taken by </li></ul><ul><li>Discharge of transmitter substance by pre-synaptic terminal </li></ul><ul><li>Diffusion of transmitter to post-synaptic membrane </li></ul><ul><li>Action of transmitter on its receptor </li></ul><ul><li>Action of transmitter to  membrane permeability </li></ul><ul><li>Increased diffusion of Na + to  post-synaptic potential </li></ul>
  31. 49. Convergence <ul><li>When many </li></ul><ul><li>pre-synaptic neurons </li></ul><ul><li>converge on </li></ul><ul><li>any single </li></ul><ul><li>post-synaptic neuron </li></ul>
  32. 50. Divergence <ul><li>Axons of most </li></ul><ul><li>pre-synaptic neurons divide into many branches that diverge </li></ul><ul><li>to end on many post-synaptic neurons . </li></ul>
  33. 51. Properties of synapse <ul><li>Neurotransmitter receptor complex </li></ul><ul><li>One-way conduction </li></ul><ul><li>Summation in Neurons </li></ul><ul><li>Facilitation of Neurons </li></ul><ul><li>Fatigue of Synaptic Transmission </li></ul><ul><li>Effect of Acidosis or Alkalosis on Synaptic Transmission </li></ul><ul><li>Effect of Hypoxia & Drugs </li></ul><ul><li>Synaptic delay </li></ul><ul><li>Convergence & Divergence </li></ul>
  34. 52. Comparison of Synapse and NMJ
  35. 53. Thank you

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