neuromuscular junction and synapses by dr.irum
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Synapse and NMJ
Dr Irum Rehman
DEFINITION
“ 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.
INNERVATION OF SKELETAL MUSCLE FIBERS
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
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.
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.
• MITOCHONDRIA – Numerous– Supply ATP – Energy source for synthesis of excitatory
neurotransmitter, acetylcholine
• DENSE BARS – Present on the inside surface of neural
membrane
• VOL TAGE GATED CALCIUM CHANNELS
– 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
MUSCLE FIBER MEMBRANE
• SYNAPTIC TROUGH – The muscle fiber membrane where it is
invaginated by a nerve terminal and a depression is formed
• SYNAPTIC CLEFT – The space between the nerve terminal and
the fiber membrane is called the synaptic space or synaptic cleft
• SUBNEURAL CLEFT – Numerous smaller folds of the muscle
membrane at the bottom of the gutter– Greatly increase the surface area.
• ACETYLCHOLINE RECEPTORS – Acetylcholine-gated ion channels– Located almost entirely near the mouths of
the sub neural clefts lying immediately below the dense bar areas
ACETYLCHOLINE RECEPTORS
• 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
• RESTING STATE – 2 Ach molecules not attached to the alpha
subunit – Channel remains constricted
• OPENED Ach CHANNEL
– 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.
• SODIUM 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
• 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
Events of Neuromuscular Junction
1. Propagation of an action potential to a terminal button of motor neuron.
2. Opening of voltage-gated Ca2+ channels.3. Entry of Calcium into the terminal button.4. Release of acetylcholine (by exocytosis).5. Diffusion of Ach across the space.6. Binding of Ach to a receptor on motor
end plate.
Examples of Chemical Agents and Diseases that Affect the Neuromuscular
JunctionMechanism that Chemicals or DiseaseAlters 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
1Excitatory 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 delayIs the minimum time required for Is the minimum time required for transmission across the synapsetransmission 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
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