The neuromuscular junction is the synapse between a motor neuron and muscle fiber. When an action potential reaches the presynaptic terminal, voltage-gated calcium channels open to allow calcium influx, triggering the release of acetylcholine (ACh) vesicles. ACh then diffuses across the synaptic cleft and binds to nicotinic receptors on the postsynaptic membrane of the muscle fiber. This opens ligand-gated sodium channels, causing sodium influx and generating an endplate potential that depolarizes the muscle fiber. If the endplate potential reaches threshold, it triggers an action potential in the muscle fiber, leading to contraction. Acetylcholinesterase then breaks down ACh to terminate the signal and allow muscle

1. NEUROMUSCULAR JUNCTION
1

2. Neuromuscular junction
(example of chemical synapse)
 Neuromuscular junction : the synapse
between motor neuron and muscle fiber is
called the neuromuscular junction
 Motor neurons : are the nerves that
innervate muscle fibers
 Motor unit : single motor neuron and the
muscle fibers it innervate
2

3. Physiologic anatomy of N.M
junction (continued)
 As axon approaches muscle , it divides
into many terminal branches and loses
its myelin sheath
 Each of these axon terminal forms
special junction ,a neuromuscular
junction with one or more muscle fiber
3

4. 4

5. Physiologic anatomy of N.M
junction (continued)
 The axon terminal is enlarged into a knoblike
structure ,the terminal botton,which fits into
shallow depression in underlying muscle fiber
5

6. 6

7. Sequence Of Events At Neuromuscular Junction
Action potential
Action potential
Ca2+
Ca2+
Presynaptic
terminal
Presynaptic
terminal
Voltage-gated
Ca2+ channel
Voltage-gated
Ca2+ channel
7
Action potentials arriving at the presynaptic terminal
cause voltage-gated Ca2+ channels to open.

8. Sequence Of Events At Neuromuscular Junction
(continued)
Ca2+ diffuse into the cell and cause synaptic vesicles to release
acetylcholine, a neurotransmitter molecule.
Ca2+
Ca2+
Synaptic
vesicle
Synaptic
vesicle
Acetylcholine
Acetylcholine
8
Ca2+ uptake into the terminal causes release of th
neurotransmitter acetylcholine into synaptic cleft , which ha
been synthesized and stored into synaptic vesicles

9. Sequence Of Events At Neuromuscular Junction
(continued)
 Ach travels across the synaptic cleft to postsynaptic membrane
which is also known as motor end plate.
Acetylcholine diffuses from the presynaptic terminal across the
synaptic cleft.
Synaptic cleft
Synaptic cleft
Acetylcholine
Acetylcholine
Presynaptic
terminal
Presynaptic
terminal
Ca2+
Ca2+
9

10. Sequence Of Events At Neuromuscular Junction
(continued)
 Motor end plate contains nicotinic receptors
for Ach , which r ligand gated ion channels
 Ach binds to the alpha subunits of nicotinic
receptors and causes conformational change.
 When conformational changes occurs ,the
central core of channels opens & permeability
of motor end plate to Na+ & K+ increases
10

11. Sequence Of Events At Neuromuscular Junction
(continued)
11
Acetylcholine bound
to receptor site opens
ligand-gated Na+
channel
Acetylcholine bound
to receptor site opens
ligand-gated Na+
channel
Ca2+
Ca2+
Voltage-gated
Ca2+ channel
Voltage-gated
Ca2+ channel
Synaptic
vesicle
Synaptic
vesicle
Postsynaptic
membrane
Postsynaptic
membrane
Acetylcholine
Acetylcholine
4
Synaptic cleft
Synaptic cleft
Action potential
Action potential
Presynaptic
terminal
Presynaptic
terminal
Na+
Na+
1
2
3
1
2
3
1
2
3
1
1
2
3
4

12. Sequence Of Events At Neuromuscular Junction
(continued)
Acetylcholine molecules combine with their receptor sites and
cause ligand-gated Na+ channels to open.
Na+
Na+
Acetylcholine bound
to receptor site opens
ligand-gated Na+
channel
Acetylcholine bound
to receptor site opens
ligand-gated Na+
channel
12

13. End plate potential
 When the ion channel on post synaptic membrane
opens both Na+ & K+ flow down their concentration
gradient.
 At resting potential net driving force for Na+ is much
greater than K+ ,when Ach triggers opening of these
channels more Na+ moves inwards than K+ out
wards, depolarizing the end plate.this potential
change is called end plate potential (EPP).
 EPP is not an action potential but it is simply
depolarization of specialized motor end plate
13

14. End plate potential (continued)
 Small quanta (packets) of Ach are released randomly
from nerve cell at rest, each producing smallest
possible change in membrane potential of motor end
plate, the MINIATURE EPP.
 When nerve impulse reaches the ending, the number
of quanta release increases by several folds and
result in large EPP.
 EPP than spread by local current to adjacent muscle
fibers which r depolarized to threshold & fire action
potential
14

15. Acetyl cholinesterase ends Ach activity at N.M
junction
 To ensure purposeful movement ,muscle cell
electrical response is turned off by
acetylcholinestrase(AchE), which degrade Ach to
choline & acetate
 About 50%of choline is returned to the
presynaptic terminal by Na+choline transport to
be reused for Ach synthesis.
 Now muscle fiber can relax ,if sustained
contraction is needed for the desired movement
another motor neuron AP leads to release of
more Ach 15