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Neuromuscular junction and synapses by DR.IRUM

Neuromuscular junction and synapses by DR.IRUM






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    Neuromuscular junction and synapses by DR.IRUM Neuromuscular junction and synapses by DR.IRUM Presentation Transcript

    • Synapse and NMJ Dr Irum Rehman
      • “ The site of connection of motor neuron with skeletal muscle making a functional contact is called as NEUROMUSCULAR JUNCTION. ”
    • Neuromuscular Junction
      • Neuromuscular Junction
      • A neuromuscular junction exists between a motor neuron and a skeletal muscle.
      • - Synapse
      • A junction between two excitable tissues.
      • Large, myelinated nerve fibers
      • Originate from large motor neurons in the anterior horns of the spinal cord
      • Each nerve fiber , branches and stimulates from three to several hundred skeletal muscle fibers
      • The action potential initiated in the muscle fiber by the nerve signal travels in both directions toward the muscle fiber ends
      • 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.
        • S ize 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.
        • Numerous
        • Supply ATP
        • Energy source for synthesis of excitatory neurotransmitter, acetylcholine
      • DENSE BARS
        • Present on the inside surface of neural
        • membrane
        • Protein particles that penetrate the neural membrane on each side 0f dense bar
        • When an action potential spreads over the terminal, these channels open and calcium ions diffuse to the interior of the nerve terminal.
        • The calcium ions, exert an attractive influence on the acetylcholine vesicles, drawing them to the neural membrane adjacent to the dense bars.
        • The vesicles then fuse with the neural membrane and empty their acetylcholine into the synaptic space by the process of exocytosis
        • Calcium acts as an effective stimulus for causing acetylcholine release from the vesicles
        • Acetylcholine is then emptied through the neural membrane adjacent to the dense bars and binds with acetylcholine receptors in the muscle fiber membrane
        • The muscle fiber membrane where it is invaginated by a nerve terminal and a depression is formed
        • The space between the nerve terminal and the fiber membrane is called the synaptic space or synaptic cleft
        • Numerous smaller folds of the muscle membrane at the bottom of the gutter
        • Greatly increase the surface area.
        • Acetylcholine-gated ion channels
        • Located almost entirely near the mouths of the sub neural clefts lying immediately below the dense bar areas
      • Acetylcholine-gated ion channels
      • Molecular weight -275,000
      • SUBUNITS
        • Two alpha, one each of beta, delta, and gamma
        • Penetrate all the way through the membrane
        • Lie side by side in a circle- form a tubular channel
        • Two acetylcholine molecules attach to the two alpha subunits, opens the channel
        • 2 Ach molecules not attached to the alpha subunit
        • Channel remains constricted
        • 2 Ach molecules attached to the alpha subunit of receptor
        • Diameter - 0.65 nanometer
        • Allows important positive ions— SODIUM, potassium, and calcium to move easily through the opening.
        • 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.
        • Far more sodium ions flow through the acetylcholine channels to the inside than any other ions
        • 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
        • Simultaneously prevents efflux of the positively charged potassium ions when they attempt to pass outward
        • 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
    • Events of Neuromuscular Junction
      • Propagation of an action potential to a terminal button of motor neuron.
      • Opening of voltage-gated Ca 2+ channels.
      • Entry of Calcium into the terminal button.
      • Release of acetylcholine (by exocytosis).
      • Diffusion of Ach across the space.
      • Binding of Ach to a receptor on motor end plate.
    • Examples of Chemical Agents and Diseases that Affect the Neuromuscular Junction
      • Mechanism that Chemicals or Disease
      • Alters Release of Acetylcholine
      • * Cases explosive release of acetylcholine * Black widow spider venom
      • * Blocks release of acetylcholine * Clostridium botulinum toxin
      • Block acetylcholine Receptor
      • * Bind reversibly * Curare
      • * Auto antibodies inactivate acetylcholine * Myasthenia gravis
      • receptors
      • Prevents inactivation of acetylcholine
      • * Irreversibly inhibits acetylcholinesterase * Organophosphates
      • * Temporary inhibits acetylcholinesterase * Neostigmine
    • Synapse
      • Definition
      • Types
      • Anatomical and Physiological
    • Properties/ Characteristics
      • A combination of neurotransmitter and a synapse will always be either
      • Excitatory
      • Or
      • 2 Inhibitory
    • One-way conduction
      • Synapses generally permit conduction of impulses in one-way i.e.
        • from pre-synaptic to
        • post-synaptic neuron.
    • Spatial Summation in Neurons
      • Excitation of a single presynaptic terminal??
        • 0.5 to 1 millivolt
      • 10 to 20 millivolts - required to reach threshold
      • Many presynaptic terminals are usually stimulated at the same time.
      • Add to one another until neuronal excitation
      • Spatial summation
        • Summing simultaneous postsynaptic potentials by activating multiple terminals on widely spaced areas of the neuronal membrane
    • Temporal Summation
      • A presynaptic terminal fire
        • changed postsynaptic potential
        • lasts up to 15 milliseconds
      • Second opening of the same channels -increase the postsynaptic potential to - still greater level
      • Successive discharges from a single presynaptic terminal
      • Rapid enough- add to one another
      • This type of summation is called Temporal summation .
    • Facilitation of Neurons
      • If the summated postsynaptic potential is excitatory………….
      • But has not risen high enough to reach the threshold
      • The neuron is said to be facilitated .
      • Another excitatory signal - excite the neuron very easily
    • Fatigue of Synaptic Transmission.
      • When excitatory synapses are repetitively stimulated at a rapid rate
      • Number of discharges by the postsynaptic neuron is at first very great
      • But the firing rate becomes progressively less in succeeding milliseconds or seconds .
      • Fatigue of synaptic transmission .
      • Protective mechanism
        • Against excess neuronal activity
          • Prevent over excitation
    • Mechanism Of Fatigue
      • Exhaustion or partial exhaustion of the stores of transmitter substance
      • Progressive inactivation of many of the postsynaptic membrane receptors
      • Slow development of abnormal conc. of ions inside the postsynaptic neuronal cell
    • Effect of Acidosis or Alkalosis on Synaptic Transmission.
      • Neurons are highly responsive to changes in pH
      • Alkalosis greatly increases neuronal excitability
        • 8.0 often causes cerebral epileptic seizures
      • Acidosis greatly depresses neuronal activity;
        • a fall in pH from 7.4 to below 7.0
        • Severe diabetic or uremic acidosis,
        • Coma
    • Effect of Hypoxia
      • Neuronal excitability is also highly dependent on an adequate supply of oxygen .
      • Cessation of oxygen for only a few seconds can cause complete inexcitability of some neurons
        • If Brain’s blood flow is temporarily interrupted,
        • Within 3 to 7 seconds , the person becomes unconscious.
    • Effect of Drugs
      • Stimulants:
      • Caffeine , Theophylline , and Theobromine ,
        • found in coffee, tea, and cocoa
      • By reducing the threshold for excitation of neurons.
      • Strychnine inhibits the action of some inhibitory transmitter substances
      • Inhibitory
      • Most Anesthetics increase the neuronal membrane threshold for excitation
    • Synaptic delay Is the minimum time required for transmission across the synapse the synaptic delay 0.5 millisecond .
      • This time is taken by
      • Discharge of transmitter substance by pre-synaptic terminal
      • Diffusion of transmitter to post-synaptic membrane
      • Action of transmitter on its receptor
      • Action of transmitter to  membrane permeability
      • Increased diffusion of Na + to  post-synaptic potential
    • Convergence
      • When many
      • pre-synaptic neurons
      • converge on
      • any single
      • post-synaptic neuron
    • Divergence
      • Axons of most
      • pre-synaptic neurons divide into many branches that diverge
      • to end on many post-synaptic neurons .
    • Properties of synapse
      • Neurotransmitter receptor complex
      • One-way conduction
      • Summation in Neurons
      • Facilitation of Neurons
      • Fatigue of Synaptic Transmission
      • Effect of Acidosis or Alkalosis on Synaptic Transmission
      • Effect of Hypoxia & Drugs
      • Synaptic delay
      • Convergence & Divergence
    • Comparison of Synapse and NMJ
    • Thank you