2. NEUROMUSCULAR JUNCTION (NMJ)
• Motor nerve fibers which
supply the muscle lose
their myelin sheath near
muscle fiber.
• Then terminal part divides
into motor nerve terminals /
end feet / synaptic knobs.
• Each end foot forms neuro-
muscular junction with a
muscle fiber at its mid-point.
• NMJ is a chemical synapse.**
3. NEUROMUSCULAR JUNCTION (NMJ)
• At NMJ, muscle fiber is
called motor end plate.
Here is an invagination
called as synaptic gutter.
• End foot fits into the
gutter to form NMJ,
but no continuity
between nerve & muscle.
• Membrane of motor end
plate is thrown into folds
sub-neural cleft.
5. NEUROMUSCULAR
JUNCTION (NMJ)
• End foot has:
Mitochondria & pre-
synaptic vesicles with
neurotransmitter:
Acetylcholine.
• Vesicles are synthesized in
cell body & then
transported to nerve
terminal & mitochondria
provide energy for it.
• In basal lamina is
Acetylcholine esterase
enzyme is present.
7. Mechanism of neuro-muscular transmission:
• Nerve impulse reaches the nerve terminal opening of voltage
gated calcium channels.
• Calcium (from ECF) enters nerve terminal agitation of some of
the synaptic vesicles (125 -150 vesicles become agitated & fuse with
membrane) release their acetylcholine into synaptic cleft by
exocytosis.
• Ach (released) binds with receptors at motor end plate
opening of Ach gated channels sodium influx end plate
potential (EPP) (which is localized potential change).
8. End plate potential (EPP)
• 50-70 mV is amplitude of EPP.
• Because of EPP Threshold for action potential is
reached (-65 mV).
• If RMP is -90 mV, then threshold is -65 mV, we need 25
mV potential change.
• Purpose of EPP is to reach the threshold of action
potential.
• So voltage of EPP is much more than required, because
required is only 25 mV. It is called as SAFETY FACTOR.
9. End plate potential (EPP) Action potential
1. Proportional to stimulus strength
(graded)
Independent of stimulus strength
(all or none)
2. Not propagated but decremental
with distance
Propagated, unchanged in magnitude
3. Exhibits summation Summation not possible
4. magnitude: low Magnitude: high
5. Refractory period: absent Refractory period: present
6. duration: Longer duration: shorter
10. How the action of
Acetylcholine is finished??
• Ach once released,
remains bound with
receptors only for 1 msec.
• Some diffuses out to ECF
& rest is hydrolyzed by
enzyme acetylcholine
esterase.
• Ach (on hydrolysis)
Choline + Acetate
11.
12. MYASTHENIA GRAVIS:
• A rare auto-immune disease.
• More common in females
• Voltage of EPP is very low (Miniature EPP) action
potential is not followed. At rest normally, a few
synaptic vesicles liberate Ach small change in EPP
(about 0.5 mV) called MEPP.
• Impulse fails to transmit through NMJ Severe
muscle weakness & fatigue.
• Auto-antibodies are produced against Ach gated
receptors & these receptors are destroyed
irreversibly.
13.
14. Clinical features of Myasthenia Gravis
• weakness of Extra-
ocular muscles ptosis
(drooping of upper
eyelids),
• diplopia (double vision)
• difficulty in Swallowing,
• weakness of Respiratory
and Facial muscles
15. TREATMENT of Myasthenia Gravis
1. Anti-cholinesterase drugs
(neostigmine,
Physostigmine) marked
improvement.
– Mechanism of action:
anticholine esterases inhibit
enzyme choline esterase
Ach not hydrolyzed more
Ach available for available
number of receptors.
2. Plasmapharesis: it may
sometimes be needed to
remove the autoantibodies
from the serum.
3. Glucocorticoids (steroids)
may also be required to
inhibit the immunity.
16. Evidence that Myasthenia Gravis is an autoimmune
disease:
1. Auto antibodies detected in patient’s blood.
2. In many of these cases, thymus is enlarged &
thymectomy is of benefit.
17. DESCRIPTION OF a typical CASE of Myasthenia
Gravis
• An 18-year-old college woman comes to the student
health service complaining of progressive weakness.
She reports that occasionally her eyelids "droop" and
that she tires easily, even when completing ordinary
daily tasks such as brushing her hair. She has fallen
several times while climbing a flight of stairs. These
symptoms improve with rest. The physician orders
blood studies, which reveal elevated levels of
antibodies to ACh receptors. Nerve stimulation studies
show decreased responsiveness of skeletal muscle upon
repeated stimulation of motor neurons. The woman is
diagnosed with myasthenia gravis and is treated with
the drug neostigmine. After treatment, she reports a
return of muscle strength.
18. EXPLANATION OF CASE
• This young woman has classic myasthenia gravis. In the
autoimmune form of the disease, antibodies are produced
to ACh receptors on the motor end plates of skeletal
muscle.
• Her symptoms of severe muscle weakness (eye muscles;
arms and legs) are explainable by the presence of
antibodies that block ACh receptors. Although ACh is
released in normal amounts from the terminals of
motoneurons, binding of ACh to its receptors on the motor
end plates is impaired. Because ACh cannot bind,
depolarization of the motor end plate (end plate potential,
EPP) will not occur, and normal action potentials cannot be
generated in the skeletal muscle. Muscle weakness and
fatigability ensue.
