The neuromuscular junction (NMJ) is a synapse between a motor neuron and skeletal muscle fiber. At the NMJ: 1) Motor neurons release acetylcholine into the synaptic cleft when an action potential arrives, which binds to receptors on the muscle fiber membrane. 2) This opens ion channels, allowing sodium ions to flow in and initiate an action potential in the muscle fiber, causing contraction. 3) The NMJ uses acetylcholine as its neurotransmitter and acetylcholine receptors to transmit signals from motor neurons to muscles in a precisely regulated process.

2. Synapse and NMJ
Dr Irum Rehman

3. DEFINITION
“ The site of connection of motor neuron
with skeletal muscle making a functional
contact is called as NEUROMUSCULAR
JUNCTION.”

4. Neuromuscular Junction
- Neuromuscular Junction
A neuromuscular junction exists between
a motor neuron and a skeletal muscle.
- Synapse
A junction between two excitable tissues.

6. 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

9. 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.

11. 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.

13. • MITOCHONDRIA
– Numerous
– Supply ATP
– Energy source for synthesis of excitatory
neurotransmitter, acetylcholine
• DENSE BARS
– Present on the inside surface of neural
membrane

15. • 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.

16. – 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

18. 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

20. • 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

22. ACETYLCHOLINE RECEPTORS
• Acetylcholine-gated ion channels
• Molecular weight -275,000

24. • 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

28. • 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.

30. • 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

31. • 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

33. Events of Neuromuscular Junction
 Propagation of an action potential to a
terminal button of motor neuron.
 Opening of voltage-gated Ca2+ 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.

35. Examples of Chemical Agents and
Diseases that Affect the Neuromuscular
Mechanism that Junction 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

36. Synapse
• Definition
• Types
• Anatomical and Physiological

37. Properties/ Characteristics
• A combination of neurotransmitter and a
synapse will always be either
3 Excitatory
Or
2 Inhibitory

38. One-way conduction
• Synapses generally permit conduction of
impulses in one-way i.e.
– from pre-synaptic to
– post-synaptic neuron.

39. 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

40. 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.

41. 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

43. 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

44. 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

45. 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

46. 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.

47. 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

48. 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

49. Convergence
When many
pre-synaptic neurons
converge on
any single
post-synaptic neuron

50. Divergence
Axons of most
pre-synaptic neurons
divide into many
branches that
diverge
to end on many post-
synaptic neurons.

51. 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

52. Comparison of Synapse and
NMJ