NEUROMUSCULAR JUNCTION

MYONEURAL JUNCTION

1. DR NILESH KATE
MBBS,MD
ASSOCIATE PROF
DEPT. OF PHYSIOLOGY
NEURO-
MUSCULAR
JUNCTION.

2. OBJECTIVES.
To draw the schematic diagram of Neuro-muscular
junction.
To describe the events of Neuromuscular
transmission
Classify neuromuscular blockers & give mechanism
of action
Name common disorders of neuromuscular junction.
Applied Aspects .
Monday, October 24, 2016

3. INTRODUCTION
Neuro-muscular
junction/ Myoneural
junction/Motor end
plate.
Junction between Motor
neuron & Muscle fibre.
Action potential from
nerve is transmitted to
muscle through this
junction.
Monday, October 24, 2016

4. STRUCTURE
Terminal button
Presynaptic
membrane
Synaptic cleft
Postsynaptic
membrane
Monday, October 24, 2016

5. PRESYNAPTIC PORTION AXON
TERMINAL
Neuron innervating
skeletal muscle fibre –
Motor Neurons
Near muscle fibre it looses
its myelin sheath & divides
into axon terminals
Each terminal is expanded
at its tip to form Synaptic
Knob ( Terminal Button)
Monday, October 24, 2016

6. PRESYNAPTIC PORTION AXON
TERMINAL
The motor neuron its axon, its
terminal with muscle fibre it
supplies – form MOTOR UNIT.
Terminal button lies in a groove-
Synaptic Trough.
Vesicles gather at specific points –
Active Zones – Membrane at
active zone modified to form
Dense Bars – contains numerous
voltage gated Ca channels.
Monday, October 24, 2016

7. SYNAPTIC CLEFT
50-100 nm wide.
Filled with extracellular fluid
Muscle fibre is covered by
basement membrane or
basal lamina.
It contains AchE (acetyl-
choline-esterase)
It hydrolyses Ach into
Acetate & Choline.
Monday, October 24, 2016

8. POST SYNAPTIC MEMBRANE
(END PLATE MEMBRANE)
It’s a part of
sarcolemma & lies
under terminal button.
It is thrown into several
folds – Junctional Folds
so increases end plate
membrane surface area.
Contains Ach-receptors
which contains voltage
gated Na channels
Monday, October 24, 2016

9. ACETYL CHOLINE RECEPTORS
Nicotinic type
15-40 millions/end plate.
Chemically gated ion
channels
Blocked by a-
Bungarotoxin.
Contains voltage gated Na
channels & allow passage
of only Cations.
Monday, October 24, 2016

10. NEUROMUSCULAR
TRANSMISSION
Def – Transmission of
impulses from motor
neuron to skeletal
muscle fibre.
Mechanism 3 parts
Presynaptic events
Synaptic events
Post synaptic events.
Monday, October 24, 2016

11. PRE-SYNAPTIC EVENTS
Main Purpose – To release acetyl choline into
synaptic cleft.
Steps –
Action potential arrive at axon terminal & Depolarize
membrane of terminal button.
Activate & open voltage gated Ca channels-Ca influx –
increases movements of Microtubules &
Microfilamants- causes migration of Neurotransmitter
vesicles to pre-synaptic membrane - DOCKING
Release acetylcholine into cleft by Exocytosis.
Monday, October 24, 2016

12. PRE-SYNAPTIC EVENTS
Quantal Release
One vesicle of acetyl
choline – Quanta
Process of release of 1
vesicle is Quantal
Release
Sir Katz, Euler &
Axelrod received
Nobel prize in 1970
for Quantal release
phenomenon
Monday, October 24, 2016

13. SYNAPTIC CLEFT EVENTS
Main Purpose –
Binding of acetylcholine
to receptors at post
synaptic membrane.
On the way some are
hydrolyzed by AchE &
remaining act on
receptors.
Monday, October 24, 2016

14. POST SYNAPTIC
EVENTS.
MAIN PURPOSE – Generate Action Potential in
sarcolemma.
Acetylcholine diffuses into cleft & bind with post-
synaptic acetylcholine receptors.
Receptors are Acetylcholine Gated Ion
Channels.
Ion channels has 5 sub uints
When 2 molecules are attached conformational
change occurs in tubular channels & open it &
increases Na influx.
Monday, October 24, 2016

15. DEVELOPMENT OF ENDPLATE
POTENTIAL
RMP of postsynaptic membrane is -80 to -90 mV.
Influx of Na channels causes local positive potential
change – END PLATE POTENTIAL.
It’s localized, Non-Propogated, Does not obey All
or None Law.
But when critical level of -60mv reached triggers
action potential in muscle fibre in both direction.
Monday, October 24, 2016

16. MINIATURE ENDPLATE
POTENTIAL
At rest, small quantity of
acetyl choline are
released from nerve
terminal.
Each vesicle release
produces weak end
plate potential about
0.5mv – Miniature End
Plate Potential.
Monday, October 24, 2016

17. REMOVAL OF ACETYLCHOLINE
BY CHOLINESTERASE
Within 1 ms by 2 ways
Mostly destroyed by
Acetylcholinestarase
in synaptic cleft.
Remaining Diffuses Out
of synaptic space & no
longer available for
action.
Monday, October 24, 2016

18. Monday, October 24, 2016
INITIATION OF THE ACTION
POTENTIAL IN MUSCLE FIBRE.

19. Monday, October 24, 2016

20. DRUGS AFFECTING
NEUROMUSCULAR JUNCTION.
Neuromuscular
Blockers – this block
neuromuscular
transmission at
junction.
Curare
Bungarotoxin
Succinylcholine and
carbamylcholine
Botulinum toxin
Monday, October 24, 2016

21. NEUROMUSCULAR BLOCKERS
Curare – active
principle D-
Tubocurarine (Cobra)
Block by combine with
Ach-receptors.
So Ach cannot act on
receptors & No End
Plate Potential develop
So these are receptor
blockers.
Monday, October 24, 2016

22. NEUROMUSCULAR BLOCKERS
Bungarotoxin –
Venom of deadly snake.
Krait.
Also block N-M junction
by combining with
acetylcholine
receptors.
Monday, October 24, 2016

23. NEUROMUSCULAR BLOCKERS
Succinylcholine &
Carbamylcholine – act like
acetyl choline & Depolarizes
post synaptic membrane
But these are not destroyed by
cholinesterase – so muscle
remain in depolarized state for
a long time.
So these block Myoneural
junction by keeping the
muscle in depolarized state.
Monday, October 24, 2016

24. NEUROMUSCULAR BLOCKERS
Botulinum Toxin –
derived from bacteria
Clostridium
Botulinum.
Block the junction by
preventing the
Release Of Acetyl
Choline from terminal
button.
Monday, October 24, 2016

25. NEUROMUSCULAR
STIMULATORS
Drugs having acetylcholine like action-
Methacholine, Carbachol & Nicotin
But these are either not destroyed or destroyed very
slowly by acetylcholinesterase so causes repeated
stimulation & continuous action of muscle – Muscle
spasm.
Monday, October 24, 2016

26. NEUROMUSCULAR
STIMULATORS
Drugs that Inactivate the enzyme Cholinesterase
(Anticholinesterase) – Neostigmine,
Physostigmine & Disopropylflurophosphate
(DFP)
So it leads to repeated stimulation & continuous action of
muscle. E.g – Laryngeal Spasm.
Monday, October 24, 2016

27. DISORDERS OF
NEUROMUSCULAR JUNCTION.
Myasthenia Gravis
Auto Immune disease.
Anti bodies are
produced against
Acetylcholine
Receptors & destroy
these channels
Monday, October 24, 2016

28. DISORDERS OF
NEUROMUSCULAR JUNCTION.
So acetyl choline
released will not
produce adequate
end plate potential &
excite muscle fibre
So patient dies of
paralysis of
Respiratory Muscles.
Monday, October 24, 2016

29. DISORDERS OF
NEUROMUSCULAR JUNCTION.
Lambert-Eaton
syndrome.
Anti bodies are
produced against
calcium channels
present on pre-synaptic
membrane – so Ca
influx decrease &
decreases release of
acetyl choline
Monday, October 24, 2016

30. Monday, October 24, 2016

31. Thank
You

32. Monday, October 24, 2016