3. NEUROMUSCULAR JUNCTION
. It is a specialized area where a Motor
Nerve ends on the Skeletal Muscle
Fiber.
. Thus, it is a Junction between a Motor
Nerve & the Muscle Fiber.
4. COMPONENTS OF N.M.J.
» 1. Prejunctional Membrane
» 2. Synaptic Cleft , or, Gutter
» 3. Motor End Plate, or, Postjunctional
Membrane
8. 1. Prejunctional Membrane
» Terminal part of Motor Nerve
» Has vesicles containing Acetylcholine
neurotransmitter.
» At terminal end, Motor nerve breaks into
several branches, supplying muscle fibers.
» The swollen part of Nerve terminal, the
Terminal button –-- fits into depression on
Muscle membrane.
9. 2. Synaptic Cleft, or, Gutter
. A potential space between Nerve
terminal & Muscle.
. Produces structural discontinuity, but
functional continuity (due to presence of
neurotransmitter , Acetylcholine) .
10. 3. Motor End Plate
» This is Post junctional Muscle membrane.
» Contains Acetylcholine receptors.
» Thrown into a number of folds termed
Subneural Clefts, or, Junctional Folds.
» These folds increase surface area – to
accommodate more no. of Ach. receptors.
13. NEUROMUSCULAR TRANSMISSION
• A.P. travelling through Nerve, arrives at Nerve
terminal .
• Opening of voltage gated Ca 2+ channels at Nerve
terminal.
• Ca 2+ , from E.C.F., enters axon terminal .
• ↑ movement & fusion of vesicles with nerve
membrane.
• Ach released into synaptic cleft (exocytosis).
• It crosses the cleft & binds to its receptor – present
on postjunctional membrane.
14. • Conformational change --- Channel opens.
• Na+ ions, from E.C.F., is poured inside muscle fiber
.
• Creates local potential inside muscle fiber –End
Plate Potential (E.P.P.). .
• EPP initiates +ve feedback on Na channel and on
reaching at firing level --- produces Action
Potential (A.P.) in mus. fiber.
• A.P. travels over sarcolemma of mus.fiber – to reach
to sarcoplasmic reticulum – for mus. contraction.
16. END PLATE POTENTIAL (E.P.P.)
» It is a Potential generated at Motor End
Plate during Neuromuscular transmission of
Impulse.
» It is a Graded, Non-propagated,
Localised Potential , without Latent period.
» It is produced due to increase in
permeability of Motor end plate to Na+ ions.
» When reaches to Firing level, it produces
Action Potential.
17. DIFFERENCE
EPP
• Local , not propagated
• Does not show All or
None Phenomenon,
Stronger the stimulus...
stronger response
• Precedes AP
AP
• Once developed, will be
propagated
• Obeys All or none Law
• Follows endplate
potential.
18. MINIATURE E.P.P.
» During rest--small quantity of Acetylcholine
is released from the pre-synaptic terminal .
» This alters the permeability of motor end
plate – to produce Depolarising change.
» This is called Miniature E.P.P.
» It is incapable of producing an Action
Potential .
19. REMOVAL OF ACETYLCHOLINE
• It is removed within few msec after
completion of its action, by two means :
(i) Destroyed by Acetylcholinesterase
enzyme .
(ii) A small amount diffuses out .
. Imp. to prevent repeated excitation of
muscle fiber.
20. DRUGS ACTING ON N.M. JUNCTION
(A)NEUROMUSCULAR STIMULATORS
(Persistent Depolarisation /Depolarising Blockers)
(I). Drugs with Ach like action :-
. Succinylcholine
. Methacholine
. Carbachol
. Nicotine
* These drugs bind to Ach. receptors in motor end plate.
* This produces prolonged depolarisation , as these
drugs are destroyed Slowly by Cholinesterase enzyme.
21. (II) Anticholinesterases : -
. Neostigmine
. Physostigmine
. These drugs destroy the enzyme Cholinesterase ,
• So prolong the action of Acetylcholine .
• Hence sustained depolarisation at motor end plate.
(III) Organophosphorus Compounds (Pesticides) :-
* Their mechanism of action is similar to action of
Physostigmine.
* Sustained depolarisation of motor end plate .
22. (III) Drugs inhibiting release of Ach :-
. Botulinum toxin
* A bacterial toxin – produced by organism
Clostridium botulinum .
(IV) Ach Antagonists :-
• Curare (D-tubocurarine)
• Bangarotoxin (Venom)
* These block the Ach receptors in motor end plate ,
by Competitive binding .
* Hence prevents action of Ach .
(B) NEUROMUSCULAR BLOCKERS: -
(Competitive Inhibition /Nondepolarising Blockers)
23. CLINICAL IMPORTANCE OF THESE DRUGS
Blocking N.M.Junction produces …
muscle relaxation .
* It helps in surgical operations. All
N.M.blockers prevent action of Ach. at
N.M.Jn. So sk.muscles do not contract .
Hence muscles tone is lost. Muscles become
Flaccid.
* It reduces movements during
electroconvulsive treatment of psychotic
patients.
24. Clinical Application of Botulinum Toxin
• Botulinum toxin is first bacterial toxin to be used
as Medicine.
(i) In conditions of muscle hyperactivity as in squint
due to spasm of extraocular muscles.
(ii) Inj. of its small doses into lower esophageal
sphincter relieves spasm in achalasia cardia.
(iii) Used for cosmetic purposes to relax muscles that
cause facial wrinkles.
25. APPLIED ASPECTS
(1) MYASTHENIA GRAVIS
Pathophysiology & Aetiology:-
* An Autoimmune disorder .
* Due to Formation of circulating auto – antibodies
against Acetylcholine receptors at motor end plate.
* So, destruction of receptors
* So, No, or week Neuromuscular transmission
26.
27.
28. Clinical Picture:-
Muscles weakness and fatigue of :
(1) Extra Ocular Muscles (Eye Musc.) :
drooping of eyelids,
(2) Throat Muscles : Difficulty in Speech,
(3) Limb Muscles : Weakness & fatigue.
(4) Respiratory Muscles (In advanced
stage): Respiratory Failure.
Treatment :-
• Anticholinesterases , e.g. Physostigmine ,
or Neostigmine .
• High doses of Cortisol
(Immunosuppresants)
29. » Also an autoimmune disorder.
» Auto antibodies damage Ca channels at
nerve terminals .
» So defective release of Acetylcholine.
» Weak neuromuscular transmission.
» Hence, muscular weakness.
•
• (2) Lambert –Eaton Syndrome
