neuromuscular junction and examples of Acetyl choline, Dopamine, GABA, Glutamate with their mechanism.

1. NEUROMUSCULAR
JUNCTION
• Submitted by : Chintan K. Patel
• Roll No.: 21
• M.Sc. Sem-1 Zoology
• Paper-404 (Unit-4)
Department of Zoology, Biomedical Technology & HG, University School of Sciences, Gujarat University,
Navrangpura, Ahmedabad.
• Submitted to : Dr. Gaurang M. Sindhav Sir

2. Outline
1. Introduction
2. Acetylcholine (ACh)
3. Dopamine
4. GABA (Gamma-amino butyric acid)
5. Glutamic acid (Glutamate)
6. References
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3. Introduction
• The neurons that stimulate skeletal muscle fibers to contract are called somatic
motor neurons. Each somatic motor neuron has a threadlike axon that extends from
the brain or spinal cord to a group of skeletal muscle fibers. A muscle fiber contracts
in response to one or more action potentials propagating along its sarcolemma and
through its system of T tubules. Muscle action potentials arise at the neuromuscular
junction (NMJ), the synapse between a somatic motor neuron and a skeletal muscle
fiber.[1]
• A synapse is a region where communication occurs between two neurons, or
between a neuron and a target cell—in this case, between a somatic motor neuron
and a muscle fiber. At most synapses a small gap, called the synaptic cleft, separates
the two cells. Because the cells do not physically touch, the action potential cannot
“jump the gap” from one cell to another. Instead, the first cell communicates with
the second by releasing a chemical called a neurotransmitter.[1]
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4. Axon terminal
Synaptic
end bulb
Neuromuscular
junction
Sarcolemma
Myofibril
Nerve impulse
Motor end plate
Synaptic
vesicle
containing
acetylcholine
(ACh)
Synaptic
cleft
(1) Neuromuscular junction[1]
(2) Enlarged view of the
neuromuscular junction[1]
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5. • At the NMJ, the end of the motor neuron, called the axon terminal, divides
into a cluster of synaptic end bulbs. Suspended in the cytosol within each
synaptic end bulb are hundreds of membrane-enclosed sacs called synaptic
vesicles. Inside each synaptic vesicle are thousands of molecules of
acetylcholine, abbreviated ACh, the neurotransmitter released at the NMJ.[1]
• The region of the sarcolemma opposite the synaptic end bulbs, called the
motor end plate, is the muscle fiber part of the NMJ. Within each motor end
plate are 30 to 40 million acetylcholine receptors, integral transmembrane
proteins that bind specifically to ACh. These receptors are abundant in
junctional folds, deep grooves in the motor end plate that provide a large
surface area for ACh. As you will see, the ACh receptors are ligand-gated ion
channels. A neuromuscular junction thus includes all the synaptic end bulbs
on one side of the synaptic cleft, plus the motor end plate of the muscle fiber
on the other side.[1]
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6. (1) Release of acetylcholine :
Acetylcholine (Ach)
Nerve impulse Synaptic end bulbs
Exocytosis of synaptic vesicles
Synaptic vesicles fuses with the
motor neuron’s PM
Liberating ACh into synaptic cleft
Diffusion of ACh between the motor
neuron & motor end plate
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7. (2) Activation of ACh receptors :
Two molecules of ACh binds to the receptor.
Opens an ion channel in ACh receptor.
Small cations (Na+) can flow across the membrane.
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8. (3) Production of muscle action potential :
Inflow of Na+ makes the inside of musle fiber more positively charged.
It triggers a muscle action potential.
Muscle action potential then propagates along
sarcolemma into the T tubule system.
Sarcoplasmic reticulum release its stored Ca+2 into the sarcoplasm.
Muscle fiber subsequently contracts.
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9. (4) Termination of ACh activity :
ACh is rapidly broken down by enzyme acetylcholinesterase (AChE).
AChE is attached to collagen fibers in the
extracellular matrix of the synaptic cleft.
AChE breaks down ACh into acetyl & choline, products
that cannot activate the ACh receptor.
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10. Ach is released
from synaptic
vesicle
Synaptic cleft
Ach binds to
Ach receptor
Junctional fold
Synaptic end bulb
Ach is broken down
Na+
Motor end plate
Muscle action
potential is
produced
(1)
(2)
(3)
(4)
(3) Binding of acetylcholine to ACh receptors in the motor end plate[1]
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11.  Dopamine
• It is synthesized in 3 steps from the amino acid Tyrosine.
• Generally involved in regulatory motor activity, in mood, motivation
and attention.
• Dopamine is inhibitory neurotransmitter.
• Low or very little amount of dopamine causes Parkinson’s Disease.
• DRUGS : Cycloset, Zelapar, Stalevo etc. [2]
 MAO = Monoamine oxidase
 COMT = Catechol-O-methyl transferase
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12. (5) Dopamine
mechanism of
action
courtesy:what-when-how.com[3]
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13.  GABA (Gamma-aminobutyric acid)
• It is synthesized directly from Glutamate.
• GABA is the most important inhibitory neurotransmitter.
• It is present in the CNS, preventing the brain from becoming
overexcited.
• Lacking of GABA in certain parts of brain results in epilepsy.
• DRUGS : Gabarone, Neurontin etc.[2]
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14. (5) GABA
mechanism
of action
14
courtesy:what-when-how.com[3]

15.  Glutamate
• It is the most commonly found excitatory neurotransmitter in the
brain.
• It is involved in the most aspects of normal brain function including
cognition, memory and learning.
• Glutamate is formed from α-ketoglutarate, an intermediate of Kreb’s
cycle.
• Excess glutamate can cause neurological disorders.
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16. [2]
(5) Glutamate
mechanism of
action
16
courtesy:what-when-how.com[3]

17. (6) Cholinergic drug mechanism of action
courtesy:nursekey.com[4]
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18. References
[1] GERARD J. TORTORA, BRYAN DERRICKSON. Muscular tissue. Principles of
Anatomy and Physiology, 12th edn. John Wiley & Sons, Inc.; 2009. p. 315-16
[2] https://www.drugs.com
[3] http://what-when-how.com
[4] https://nursekey.com
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