St. Luke’s College of Medicine – William H.

Quasha Memorial
PHYSIOLOGY BLOCK 1

Lecture: 6 - Neuromuscular Transmission Date: August 7, 2015

Lecturer: Irving Tan, MD Trans Team: Saballo, Salenga, Santos, F., Santos, J.

Topic Outline
I. Origin of Efferent Motor Neuron and Its Types
II. The Neuromuscular Junction
III. Formation and Release of Acetylcholine
IV. Fate of Acetylcholine in the Neuromuscular
Junction
A. Ach binds to Ach-receptors on the post-synaptic
membrane
B. Recycling of choline back to the pre-synaptic
terminal
V. End Plate Potential
VI. Summary of Neuromuscular Transmission

I. Origin of Efferent Motor Neuron and Its Types

Primary motor cortex – origin of stimulus that control the
voluntary action of the skeletal muscles
Efferent motor neuron – innervates the skeletal muscle fiber;
located at the anterior/ventral horn of the spinal cord;
2 types:
 Alpha motor neurons – innervates the extrafusal or
regular muscle fibers; their axons terminate with synapses
called neuromuscular junctions or end plates.
 Gamma motor neurons – innervates the intrafusal
muscle fibers; smaller than α motor neurons
o Intrafusal muscle fibers – multiply innervated and
receive both sensory and motor innervations
Motor unit – consists of the motor nerve and all muscle fibers
innervated by the nerve
II. The Neuromuscular Junction
Neuromuscular junction
– junction of nerve endings with the muscle fiber near its
midpoint (assures that action potential travels in both
directions in the muscle)
Figure 2. Neuromuscular junction
III. Formation and Release of Acetylcholine
*Recall: Synaptic transmission
 Acetylcholine is synthesized in the cytosol and is rapidly
absorbed into synaptic vesicles
 Vesicles are formed by the Golgi apparatus in the cell
body of the motorneuron in the spinal cord. They are
transported to the axon terminal through axoplasmic
streaming
 About 10 000 molecules of acetylcholine are concentrated
inside a single vesicle
General Mechanism of Acetylcholine Release
1. Action potential depolarizes the presynaptic (neuron)
terminal.
2. Voltage-gated Ca2+ channels in presynaptic terminal open
-> Ca2+ enters the axon terminal membrane
3. Rise in Ca2+ triggers the fusion of vesicles containing
acetylcholine to the presynaptic terminal membrane
o SNARE proteins– SNAP (soluble NSF attachment
protein)receptor proteins on the membrane of vesicles
(v-SNARE) and presynaptic terminal membrane (t-
SNARE)
-mediates exocytosis of neurotransmitters (i.e.
Acetylcholine) by fusing the presynaptic terminal
membrane and vesicles
4. About 125 vesicles of acetylcholine are then expelled in
the synaptic cleft through exocytosis.

Figure 1.Single motor unit

Parts of the Neuromuscular Junction

 Axon terminal – end of axon where the synaptic vesicles
are released
 Synaptic vesicles – contain the neurotransmitter
(acetylcholine)
 Synaptic gutter/trough –invaginated membrane
 Synaptic space/cleft – space between the terminal and
muscle membrane; has large quantities of the enzyme
acetylcholinesterase
 Motor end plate – complex of branching nerve terminals
that invaginate into the surface of the muscle fiber, but lie Figure 3. Release of Acetylcholine
outside the muscle fiber plasma membrane. It is insulated
by one or more Schwann cells that insulate it from the Recycling of Vesicles in Synaptic Transmission
surrounding fluid 1. Clathrin (a contractile protein) coats the plasma
 Sarcolemma – cell membrane of the muscle fiber membrane, which then pinch off to form coated pitsin
 Subneural folds/clefts – smaller folds of the sarcolemma the membrane of the presynaptic terminal.
at the bottom of the synaptic gutter/trough; to increase 2. This protein contract and causes the “coated pits” to break
surface area away to the interior of the membrane and thus forming
 Sarcomere – contractile unit of in the skeletal muscle new vesicles.
 Sarcoplasmic reticulum – the endoplasmic reticulum of
the muscle; surrounds the sarcomere  Botulinum toxin – bacterial poison that decreases
quantity of acetylcholine released
 Transverse tubules/T-tubules – invagination in the
sarcolemma which pass the muscle fiber near the
IV. Fate of Acetylcholine in Neuromuscular Junction
sarcomeres
 Terminal cisternae/lateral sac – portion of sarcoplasmic A. Acetylcholine binds to acetylcholine receptors on the
reticulum nearest the T-tubules post-synaptic membrane
 Acetylcholine receptors or acetylcholine-gated cation
channels consist of 5 subunits: 2 α, 1 β, 1 γ, 1 δ subunits

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 the Ach-gated channels only allow cations to pass through
because of its negatively charged interior
 Curare – a drug that blocks action of acetylcholine on its
receptors
Figure 4. Acetylcholine receptor
 Depolarization of the sarcolemma
1. Acetylcholine binds to the alpha subunits of the
acetylcholine receptor
2. This causes conformational change in acetylcholine
receptor which enlarges its negatively-charged center
3. Sodium ions and other cations pass and enter the muscle
fiber
4. Influx of cations causes depolarization of the motor end
plate
5. Action potential is initiated on sarcolemma
Figure 5. Binding of acetylcholine to acetylcholine receptor
Importance of the T-tubule sarcoplasmic reticulum system
– T- tubules run transverse to the myofibrils and are
adjacent to the terminal cisternae; Ca2+ is therefore in
the immediate vicinity of the myofibrils
– transmission through the tubules allows maximum
muscle contraction as current can penetrate deep into
the muscle
– conformational changes in voltage-sensing
dihydropyridine receptors in the T-tubules opens the
Ca2+ channels of the terminal cisternae
Figure 6.T-tubule sarcoplasmic reticulum system
B. Recycling of choline back to the pre-synaptic terminal
1. Acetylcholine at the receptor is broken down by
acetylcholinesteraseto form acetate and choline
o Acetylcholinesterase – believed to be in the spongy
layer (connective tissue) at synaptic space
2. Choline is shuttled back to the presynaptic membrane
3. Choline is added into the vesicle to undergo specific
reaction and form acetylcholine
 This process, along with the diffusion of acetylcholine from
the synaptic space, prevents its build-up which may cause
prolonged muscle contraction.
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BLOCK 1
Figure 7.Breakdown of Acetylcholine
V. End Plate Potential
1. Action potential is initiated due to depolarization of the
motor end plate
2. Action potential is propagated along the sarcolemma and
down the T-tubules
3. T-tubules undergo conformation which allows calcium ions
on the terminal cisternae to open
4. Calcium ions are released from the terminal cisternae
5. Muscle contracts
 Safety factor: impulse that arrives at the junction causes
thrice as much end plate potential as required to stimulate
the fiber
 Fatigue of the neuromuscular junction may happen when
the rate of stimulation of the nerve is greater than 100
times per second
Excitation-Contraction Coupling
- process of converting electrical stimulus to mechanical
response
- process wherein action potential in the sarcolemma is
propagated to T-tubules which in turn allows the terminal
cisternae to release Ca2+ ions to the sarcoplasm, eliciting
muscle contraction
VI. Summary of Neuromuscular Transmission
Figure 8.Neuromuscular junction and mechanism of muscle
contraction (elaborated in the next lecture: Muscle Physiology)
1. Action potential arrives at axon terminal
2. Calcium ions enter axon terminal
3. Synaptic vesicles fuse to membrane of axon terminal
4. Acetylcholine released to the synaptic cleft
5. Acetylcholine binds to receptor sites on the motor end plate
6. Motor end plate becomes depolarized
7. Action potential is initiated on sarcolemma
8. Action potential propagates along sarcolemma and down T-
tubules
9. Calcium ions are released from terminal cisternae
10. Muscle contracts
IV. References
 The brilliant mind of Dr. Tan and his picture slides
 Guyton and Hall Textbook of Medical Physiology. 12 thed.
 Berne and Levy Physiology. 6thed.
V. QUIZ
1. What are the two mechanisms involved in the destruction
or removal of acethycholine in the synaptic space?
2. True or False: action potential opens voltage gated
calcium ions that leads to the synthesis of acetylcholine
3. A ___________ is the junction between an axon terminal
and the plasma membrane of the motor end plate of a
muscle fiber
4. What is the function of the negative charges at the channel
mouth of the acetylcholine-gated channels?
 PHYSIOLOGY BLOCK 1

5. Is the acetylcholine receprot a ligand-gated ion channel or

a voltage-gated ion channel?
6. Which of the following drugs stimulate the muscle fiber by
acetylcholine like action?
a. Nicotine
b. Neostigmine
c. Carbachol
d. A and C
7. Why doesthe acetylcholine-gated ion channel only allow
the passage of sodium ions?
8. Why does the acetylcholine-gated ion channel only allow
the passage of sodium ions?
9. True or False: At the beginning of and end plate potential,
na+ current through the acetylcholine receptor channels is
about equal to the K+ current
10. At the neuromuscular junction
a. The release of acethylcholine from the motor neuron
causes an end plate potential in the motor end plate
b. acetylcholinesterase inhibits repolarization on the
motor end plate
c. summation of end-plate potentials is required to
trigger an action potential in the muscle membrane
d. A and B
e. A and C
11. Differentiate curare and botulinum toxin

Answers:
1. a) destruction by acetylcholinestrase; b) diffusion
2. True
3. Neuromuscular junction
4. Prevents passage of negative ions such as Cl-
5. Ligand-gated channel
6. D
7. concentration of Na+ ions is greater in the ECF; the
negative potential inside the muscle membrane pulls the
positive ions inside the fiber but prevents the efflux of K +
ions from inside
8. False. Na+ current > K+ current: conductance to Na+ and
K+ are similar but the driving force on Na+ is much greater
than K+
9. E
10. Curare: competes with acetylcholine for the acetylcholine
receptor sites, effectively blocking the opening of
acetylcholine-gated ion channel
Botulinum toxin: decrease acetylcholine release by the
nerve terminals

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