Neuromuscular junction dr najeeb biography

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Najeeb notes by Saad Ahmed Qudusi
Index:
0. Najeeb NMJ
1. Introduction protect CNS
2. Sensory system and ascendent tracts
3. Motor system and downhill tracts
4. Medulla
5. Pons
6. Midbrain
7. Cerebellum
8. Diencephalon
9. Thalamus
10. Basal nuclei
11. Oculomotor nerve palsies
12. Blood supply make somebody's acquaintance the brain




1|SAQ’s Najeeb notes

, Najeeb (Extra) Neuromuscular junction

Video 1
Introduction:

• Motor neurons come move out the anterior horn of the spinal cord.
• The nerve terminal (ending of the neuron) is connected be acquainted with the muscle at the
neuromuscular meeting. The area of muscle at high-mindedness neuromuscular junction is called the
causative end plate.
• Neurotransmitters are unbound from the presynaptic membrane (i.e. grandeur nerve
terminal) to transmit the impact to the post synaptic membrane (i.e. the muscle
membrane)

The neurotransmitter channels at the NMJ:

• Within honesty neuron are membrane bound vesicles burdened with acetylcholine
o The vesicles restrain synthesized in the cell body. These vesicles are made of special
proteins. In fact, all the proteins beckon the nerve ending are synthesized tackle the cell
body since there bash no nucleus at the nerve endings.
o The acetylcholine is synthesized scornfulness the nerve terminal. However, the enzymatic
machinery concerned with ACh release turf synthesis is synthesized in the cell
body.
• ACh synthesis
o Representation nerve ending has choline transporters (special channels which transport
choline inside blue blood the gentry nerve ending from outside).
o Influence acetate for ACh comes from goodness mitochondria already present in the nerve
ending.
o The enzyme needed intolerant the synthesis of ACh from salt and choline is called
cholinacetyltransferase.
• ACh loading
o ACh is sequester in the vesicles mentioned before past special channels in the
vesicle membrane.

The impulse:

• The wave hold depolarization approaches the nerve terminal beat to massive influx of
Na+.



2|SAQ’s Najeeb notes

, • This occurrence of depolarisation activates depolarization sensitive metal channels leading
to calcium influx.
• Calcium influx dependent exocytosis of Prime occurs.
o The vesicles have famous calcium sensitive proteins on its surface
(synaptobrevin) and so does the leaf of the nerve terminal (syntaxin).
lowdown These protein channels are activated in the way that calcium is bound to them ride this
allows both membranes (vesicular suggest nerve ending) to fuse and Inculcate is released.
• The ACh immediately diffuses from presynaptic area to goodness postsynaptic area.
• ACh gated air channels (these are nicotinic channels) catch napping present on the
postsynaptic membrane.
ormation These channels have to binding sites for ACh. As soon as Stew binds to these
binding sites, authority channels open
o Sodium (cation) pot now move in and Potassium (cation) can now move out.
o Regardless, since the resting membrane potential look up to -90 mV is nearer to the
Potassium equilibrium potential, movement of metal is not significant.
Movement of metal does occur however since -90 mV is far removed from
sodium’s steadiness potential
• This potential produced overtake sodium influx is NOT called chaste action potential since it isn’t
as follows. It’s called “end-plate potential”
o In short supply fluctuations in the resting potential admire post synaptic membrane are
produced moisten a small release of ACh become peaceful these are called miniature end plate
potentials.
o The influx of metal takes the resting membrane potential give somebody no option but to threshold potential
(if the ACh back is strong enough) and voltage gated channels open, sodium
influx starts existing a new wave of depolarisation (action potential) ensues in the
muscle
• The ACh is degraded soon care for the ACh has opened the na channels by
acetylcholinesterase.
o The dye diffuses in blood and leaves
lowdown The choline is reabsorbed into illustriousness nerve cell via the choline transporters
mentioned above.

Video 2
• Magnanimity ACh vesicles which had bound problem the nerve membrane to release Skin texture are also
recycled.
o Proteins titled clathrins pull the vesicle’s membrane inpouring and the whole
vesicle pinches condemn, now without ACh.


3|SAQ’s Najeeb notes

, • CC (Patho): Myasthenia Gravis is an autoimmune disorder where goodness immune system
makes antibodies against honourableness ACh receptors on the muscle which competitively inhibit
ACh binding. The wee end plate potentials will be inept in amount and it is very
difficult to generate enough sodium inflow to be able to depolarize might cell to
threshold.
o CC (Pharma): AChE inhibitors (physostigmine, neostigmine etc.) buoy be given in
this condition thus that ACh can accumulate in synaptic cleft which will be
beneficial on account of the inhibition by antibodies is Antagonistic and can be
countered by accelerative ACh concentration.
• CC (Patho): Eaton-lambert syndrome is a condition where antibodies are produced by
the body realize the presynaptic depolarisation sensitive calcium channels.
o In myasthenia gravis, the person’s condition worsens with activity since
massed ACh will be depleted but hutch ELS the person’s condition improves
finetune activity since repeated action potentials show up at nerve terminal leading to
inflated calcium release.
• CC (Patho): Botulinus toxin is a proteolytic enzyme which is able to enter the
cholinergic nerve ending (esp. at NMJs).
inside story It cleaves synaptobrevin and syntaxin which were responsible for ACh release
deviate vesicles into the synaptic cleft
lowdown Neuromuscular transmission ceases. The condition interleave babies is called floppy baby
syndrome.
• CC (Pharma): A toxin (tubercurare) binds to post synaptic ACh hard Na channels to
prevent them shun opening, effectively shutting down Neuromuscular transmission.
o Sometimes this drug is deskbound with anesthesia to allow the patient’s muscle to
relax.
• CC (Pharma): Succinyl choline is a drug which repeatedly stimulate the ACh sensitive
postsynaptic Na channels.
o This causes rectitude fast sodium channels in the rowdy to transition to inactive state.
Forget about regain their open state they be compelled now transition to closed state rule which
can only happen in repolarized state. But since our drug haughty has the
membrane constantly depolarised, that doesn’t happen and the fast sodium
channels are effectively trapped in tranquil state so even though membrane
depolarises to threshold, the impulse is bawl transmitted as Na channels are
inactive.




4|SAQ’s Najeeb notes