NEUROMUSCULAR JUNCTION

Dr. Mustafa Al-Shehabat MSc, Ph.D.

Department of Physiology and Biochemistry

School of Medicine , M2 5th floor
mashehabat@just.edu.jo

1
 Synapse:
a functional connection between a neuron Axon of motor neuron
and another cell

1. Chemical synapse, i.e. neuromuscular junction

Neuromuscular junction
 NEUROMUSCULAR JUNCTION

Is the junction (synapse) between a nerve (motor neuron) and a muscle cell (muscle fiber)

Motor neuron is the neuron that innervates a muscle fiber

Physiological anatomy of the neuromuscular junction

1. Terminal button
2. Motor end plate
Sequence of events at the neuromuscular junction
 Sequence of events at the neuromuscular junction

1. Arrival of the action potential:

causes depolarization of the
terminal that opens voltage gated 1
Action potential
calcium channels allowing calcium
influx.
2
Ca2+
2. Calcium influx Presynaptic
terminal
Voltage-gated
Ca2+ channel
Sequence of events at the neuromuscular junction

4. Calcium influx into the terminal causes synaptic

vesicles to fuse with the synaptic membrane and to Ca2+
release its contents (neurotransmitter acetylcholine )
Synaptic
into the synaptic cleft by exocytosis vesicle

Acetylcholine

Ca2+ diffuse into the cell and cause synaptic vesicles to rele
acetylcholine, a neurotransmitter molecule.
Sequence of events at the neuromuscular junction

5. Ach diffuses in the synaptic cleft and binds its receptor on the motor end plate

Motor end plate contains nicotinic receptors for Ach ,

Action potential
which are ligand gated ion channels
Ca2+
1
Presynaptic
Ach binds to the nicotinic receptors and causes Synaptic
vesicle
terminal

conformational change. Voltage-gated

Ca2+ channel Synaptic cleft
2

When conformational changes occurs ,the central

core of channels opens & permeability of motor end 3

plate to Na+ & K+ increases Acetylcholine Postsynaptic

membrane
Na+
Acetylcholine bound
to receptor site opens
ligand-gated Na+ 44
channel
Sequence of events at the neuromuscular junction

Na+
Acetylcholine bound Motor end plate
to receptor site opens
ligand-gated Na+
channel

Acetylcholine molecules combine with their receptor sites and

cause ligand-gated Na+ channels to open.causing local depolarization at
the motor end plate called end
plate potential EPP
End plate potential EPP

The local depolarization of the postsynaptic membrane in response to opening of

Ach receptors

EPP stimulates the adjacent areas (other than the end

plate) and initiates an action potential by opening of voltage
Gated sodium channels
Acetyl cholinesterase AchE
terminates the effect of Ach at
neuromuscular 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 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
Myasthenia gravis:
autoimmune disease where antibodies against the Ach receptors are produced.
Which consequences do you expect? … weakened EPP and thus muscular
weakness

How do you think you can ameliorate the situation?... Neostigmine

Muscle Tissue Types
Skeletal

Cardiac

Smooth
 Muscle Comparison Chart
Muscle Special
Tissue Cell Shape Striae Nucleus Control structures

Multi-
Skeletal Cylindrical Yes nucleate & Voluntary none
peripheral

Cardiac Cylindrical & Uninucleate Intercalated

Yes Involuntary
branched & central discs

May be
Uninucleate
Smooth Fusiform No Involuntary single-unit or
& central
multi-unit
Skeletal Muscle
Functional Anatomy
 Skeletal muscle

Physiologic anatomy of skeletal muscle

 Skeletal Muscle Fiber

Banded appearance

The striations are arranged longitudinally into myofibrils

 Z line A band I band
Portion
of myofibril

M line H zone

Sarcomere
Thick filament A band I band
Thin filament

Cross M line H zone Z line

bridges

Myosin Actin

Thick filament Thin filament Sherwood

Z line Z line
General mechanism of muscle contraction
Calcium Release in Excitation-Contraction
Coupling
T Tubules and Sarcoplasmic Reticulum
Actin structure
• Thin filaments are composed
of
– g-actin molecules in
a helical arrangement
• Contain myosin binding
sites
– nebulin
• Filament that forms
internal support and
attachment for actin
– tropomyosin filaments
– troponin (complex of three
molecules)
attached to tropomyosin
• Has binding sites for Ca 2+

Figure 12.4
Sarcomere Contraction
 Muscle Contraction: Mechanical Events

Acto-myosin cross bridge cycle

• Myosin heads bind to actin filaments

• ATP hydrolysis allows the myosin head to walk along the actin filament

• Myosin is an actin-activated AtPase

Rigor Mortis : In the absence of ATP, the muscles remain in a contraction state as the
myosin head stayed attached to actin ( ATP is the cause of separation) and this what
Happens the muscles of the body after death
Watch the Cross Bridge Cycle animation. 

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