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Pawlose Ketema
Special Characteristics of Muscle Tissue
Physiology of Skeletal Muscle Fibers
For skeletal muscle to contract
• Activation (at neuromuscular junction)
Excitation-contraction coupling
Nerve Stimulus of Skeletal Muscle
Stimulated by motor neurons of the somatic nervous
Axons of the motor neurons travel to muscle cells
(branch profusely as they enter muscles)
Each branch forms a neuromuscular junction with a
single muscle fiber
Formation of the Neuromuscular
The neuromuscular junction is formed by the
following components:
 Axonal
endings containing small synaptic vesicles that
contain acetylcholine (ACh)
 The motor end plate of a muscle, which is a specific
part of the sarcolemma that contains ACh receptors
Though the axonal ending and the motor end plate
appear close, they are separated by a space
called the synaptic cleft
Neuromuscular Junction
Events at Neuromuscular Junction
Events at Neuromuscular Junction
Destruction of ACh
ACh bound to ACh receptors is quickly destroyed by
the enzyme acetylcholinesterase
This destruction prevents continued muscle fiber
contraction in the absence of additional stimuli
Breaks ACh into acetate and choline  Acetate
and Choline is transported back into axon terminal
and used to make more ACh.
Fate of Neurotransmitters
Post synaptic binding
Systemic circulation
Myasthenia Gravis
Chronic autoimmune neuromuscular disorder that is
characterized by weakness of voluntary muscle
that block ACh receptors  inhibiting the
excitatory effects of the ACh at nicotinic receptors
 Genetic in neuromuscular junction
 Antibodies
Treatment: ACh inhibitors (make a correction it
should be ACHE)
Therapeutic Significance
Pharmacologic Target
Termination of action
Receptor effect
Generation and Propagation of AP in
Skeletal Muscle
Binding of ACh to ACh
receptors opens ligand
gated channels Na+
influx and K+ efflux.
Na+ driving force > K+ force
Change in membrane
potential  interior
sarcolemma becomes less
negative depolarization
(end plate potential)
Generation and Propagation of AP in
Skeletal Muscle
End plate potential
ignites an AP 
spreading to adjacent
membrane areas 
opening voltage-gated
Na+ channels
Once threshold is
reached an AP is
AP propagates in all
directions  opening
more Na+ channels
Generation and Propagation of AP in
Skeletal Muscle
As a consequence of
changes in membrane
potential, repolarization
Na+ channels close and K+
channels open
K+ diffuses out of the cells
Cell is in a refractory
period  cell cannot be
stimulated until
repolarization is complete
AP is unstoppable 
results in contraction of
Action Potential of Skeletal Muscle
Excitation-Coupling Contraction
Excitation-Coupling Contraction
Rigor Mortis
Recognizable sign on death
After death  cease in respiration deplete
oxygen that is used to make ATP
ATP is used to separate the cross-bridges during
In rigor mortis, the myosin head remains bound to
the active site  muscle unable to relax
Eventually, the muscle proteins break down after
death and the cross-bridge breaks
Diseases of Muscle Contraction
Botulism/Botox: bacteria Clostridium botulinum
(grows in improperly canned foods) produces
botulinum toxin: toxin prevents release of Ach at
neuromuscular junction, results in flaccid paralysis
Tetanus: Clostridium tetani (grows in soil) produces
tetanus toxin: toxin causes over stimulation of motor
neurons, results in spastic paralysis
Myasthenia gravis: autoimmune disease, causes
loss of Ach receptors, muscles become nonresponsive
Contraction of Skeletal Muscles
The force that exerted by a contracting muscle on an
object is called muscle tension. The opposing force
exerted on the muscle by the weight of the object to be
moved is called the load.
The two types of muscle contraction are similar
 Isometric contraction – increasing muscle tension (muscle
does not shorten during contraction)
Tension develop but the muscle does not move
Isotonic contraction – decreasing muscle length (muscle
shortens during contraction)
Tension develops and overcomes the load  muscle
The Motor: The Nerve-Muscle Functional Unit
A motor unit is a motor
neuron and all the muscle
fibers it supplies
The number of muscle
fibers per motor unit can
vary from four to several
Muscles that control fine
movements (fingers, eyes)
have small motor units
Large weight-bearing
muscles (thighs, hips) have
large motor units
Muscle Twitch
A muscle twitch is the response of
a muscle to a single, brief threshold
The three phases of a muscle twitch
Latent period – first few milli-seconds after
stimulation when excitation-contraction
coupling is taking place
Period of contraction- cross bridges actively
form and the muscle shortens
Period of relaxation- Ca2+ is reabosorbed
into the SR, and muscle tension goes to zero
Graded Muscle Response
Graded muscle responses are:
 Variations
in the degree of muscle contraction
 Required for proper control of skeletal movement
Responses are graded by:
 Changing
the frequency of stimulation
 Changing the strength of the stimulus
Muscle Response to Varying Stimuli
A single stimulus results in a single contractile response – a
muscle twitch
Frequently delivered stimuli (muscle does not have time to
completely relax) increases contractile force – wave
More rapidly delivered stimuli result in incomplete tetanus
If stimuli are given quickly enough, complete tetanus results
Muscle Response: Stimulation Strength
Sub-threshold stimuli -that
produce no observable
Threshold stimulus – the
stimulus strength at which the
first observable muscle
contraction occurs
Maximal stimulus – the
strongest stimulus that
increases contractile force
The point at which all the
muscle’s motor units are
Increasing the stimulus
intensity does not produce a
stronger contraction
Stimulus Intensity and Muscle Tension
Force of contraction is
precisely controlled by
multiple motor unit
This phenomenon, called
recruitment, brings more
and more muscle fibers
into play
The recruitment process
is dictated by the size
Why is the size principle
Isotonic Contractions
In Isotonic contractions, the
muscle changes length and
moves the load.
The two type of isotonic
contractions and concentric
and eccentric
Concentric contractions – the
muscle shortens and does
Eccentric contractions – the
muscle contracts as it
Isometric contractions:
Tension increases to the
muscle’s capacity, but the
muscle neither shortens nor
Occurs if the load is greater
than the tension the muscle is
able to develop
Muscle Metabolism: Energy for
ATP is the only source used directly for contractile
Muscles store a limited amount of ATP (~4-6
seconds worth)
ATP regenerated within a fraction of a second via
these pathways:
 Direct
 Anaerobic glycolysis
 Aerobic respiration
Direct Phosphorylation of ADP by
Creatine Phosphate (CP)
CP is a unique highenergy molecule stored in
muscles (used during
vigorous exercise)
Used while body
regenerates ATP while the
metabolic pathways adjust
to the suddenly higher
demand for ATP
Muscle cells store 2-3
more times CP than ATP
Together CP and ATP
provide maximum muscle
power for 15 seconds
Anaerobic Pathway: Glycolysis and
Lactic Acid Formation
Used when ATP and CP stores are
ATP is generated by breaking down
(catabolizing) glucose obtained from the
blood or glycogen stored in the muscle
Pyruvic can produce ATP depending on its
environment (presence or absence of O2)
Use in the presence and absence of O2 but
does not use it
Glucose  2 pyruvic  release 2 ATP
Under anaerobic conditions, lactic acid, the
end product, is formed.
Typically, lactic acid diffuses out of the
muscles into blood stream  used by liver
and kidney and converted into pyruvic acid or
Too much lactic acid creates the burning
sensation felt during exercise
Aerobic Respiration
Since CP is limited, the muscle must
metabolize nutrients to transfer energy
from foodstuff  ATP
Include glycolysis (continuation of
anaerobic respiration)
Aerobic respiration takes place in the
mitochondria and requires oxygen
Initial exercise – glycogen provides most
of the energy
0-30 min of exercise – glucose and
fatty acid are major sources of energy
30 min and above – fatty acid are the
major fuel
Aerobic respiration yields ~ 32 ATP
per glucose but it is slow due to the
many steps and the high demand for
oxygen and nutrients to keep going
Overview of ATP Pathways
Force of Contraction
The force of contraction depends on the number of myosin cross
bridges that are attached.
The 4 factors that affect
the force of contraction:
The number of muscle
fibers stimulated
Relative size of fibers
Frequency of
Degree of muscle
Factors that Affect the Force of
The number of muscle fibers stimulated
The more motor units recruited, the greater the muscle force
Relative size of fibers
The bulkier the muscle The more tension  greater the
Regular resistance exercise increases muscle force by causing
the muscle to hypertrophy (increases muscle size)
Factors that Affect the Force of
Frequency of Stimulation
Rapid stimulation summation
 leads to stronger contraction
Degree of muscle strength
muscles contract strongest when
muscle fibers are 80-120% of
their normal resting length
Muscle Fiber Type: Functional
Speed of contraction – determined by speed in
which ATPases split ATP
 The
two types of fibers are slow and fast
ATP-forming pathways
 Oxidative
fibers – use aerobic pathways
 Glycolytic fibers – use anaerobic glycolysis
These two criteria define three categories – slow
oxidative fibers, fast oxidative fibers, and fast
glycolytic fibers
Muscle Fiber Type: Speed of
Slow oxidative fibers contract slowly, have slow
acting myosin ATPases, and are fatigue resistant
Fast oxidative fibers contract quickly, have fast
myosin ATPases, and have moderate resistance to
Fast glycolytic fibers contract quickly, have fast
myosin ATPases, and are easily fatigued