Collin County Community College
BIOL 2401
Muscle Physiology
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Energy Metabolism
Energy metabolism deals with all the components and
processes within a cell that interact to provide the
necessary energy to the energy consuming elements
of a cell.
The energy requiring processes in a muscle cell are of
course those that consume ATP e.g. the contractile
elements.
A contracting muscle cell requires about 2500 ATP
molecules per second. However, ATP is a very
unstable component. The cell only has a small quantity
available for direct use.
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Energy Metabolism
So how does a muscle cell
deal with continued demand
during contraction ?
Three different processes
are involved and provide
the ATP needed for
contraction.
Aerobic Metabolism
Glycolysis
Creatine Phosphate System
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Energy Metabolism
1. Aerobic respiration
This is the process where the energy of nutrients is
completely released by means of several metabolic
pathways.
The final process occurs in mitochondria where, in the
presence of oxygen, ATP is formed
It requires the continuous delivery of oxygen and
nutrients to the tissues and cells ( thus requires an
efficient and non-occluded blood vessel network to the
tissues)
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2
Energy Metabolism
C6H12O6 + 6 O2 + 38 ADP + 38 Pi
6 CO2 + 6 H2O + 38 ATP
The typical nutrient is glucose (6 carbon molecule).
•  comes from the diet
•  from stored glycogen ( animal equivalent of starch)
Steps in Aerobic Metabolism & Oxidative Phosphorylation
•  Glucose is oxidized in glycolysis to Pyruvate
•  Pyruvate enters the mitochondria and is completely oxidixed to
CO2 in the Krebs Cycle. Energy (electrons and H+ ) is transferred
onto NAD+ and FAD+, forming NADH and FADH
•  NADH and FADH go through the electron transport chain and ATP
is generated via proton gradients and the ATPsynthase.
•  The final electron acceptor in the ETC is oxygen !
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Energy Metabolism
O2 used in this process
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Energy Metabolism
2. Anaerobic Glycolysis
In the absence of oxygen, the mitochondria can’t oxidize the pyruvate.
The pyruvate is converted into lactic acid by means of Lactic Acid
Dehydrogenase (LDH)
Occurs in muscles with a high energy demand ( usually during
vigorous activity).
Depending on the muscle type, exercise results in the muscle to
bulge up which constrict the blood supply to the muscles.
This reduces blood flow and reduces oxygen and nutrient supply. The
lack of oxygen deviates the aerobic pathway into a lactic acid
producing pathway.
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Energy Metabolism
No O2- no ETC activity-No
Kreb cycle turnover-Pyruvate
not used in Mitochondria
x
x
x
no
no
Lactic Acid production
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Energy Metabolism
3. Creatine Phosphate
Creatine Phosphate is a high energy reservoir made from
ATP and creatine, catalyzed by the enzyme Creatine
Kinase
ATP + Creatine
ADP + CrP
Creatine Kinase (or Phosphocreatine Kinase) is an
equilibrium enzyme ; the reaction it catalyzes is driven
by mass action ratios.
•  In other words, if ATP increases, the reaction is driven to the
right, making CrP.
•  If ATP decreases (or CrP increases), the reaction is driven to
left, making ATP .
the
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Energy Metabolism
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Energy Metabolism Summary
•  During resting conditions, oxygen supply is plenty and energy
demands are low. Most energy is supplied by Ox.Phos. In addition,
muscle converts extra ATP into CrP and extra glucose into
Glycogen
•  During increased demands of energy, such as increased contractile
activity, demand may outpace production via Ox.Phos. At this point,
glycolysis and CrP system will be used more in order to meet the
demands.
•  At highest activity and demand, most energy will come from
glycolysis and production of lactic acid will increase. Glucose will be
provided by breakdown of the glycogen reserves. CrP will be
exhausted quickly and continued activity depends on glycogen
stores and the efficiency in getting rid of lactic acid.
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Energy Metabolism Summary
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Energy Metabolism
Most muscles have poor supply of mitochondria. Their capacity to
generate ATP via oxidative phosphorylation is thus limited. Muscles
thus will generate Lactic acid quite fast when very active.
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Energy Metabolism and Exercise
Aerobic endurance refers to the length of time muscle
contraction uses aerobic metabolism.
Anaerobic metabolism refers to the moment oxygen
becomes limiting.
In general, activities that depend on anaerobic metabolism cannot
be sustained for prolonged periods of time ! The shift from aerobic
to anaerobic is when lactic acid start to accumulate in muscles.
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Energy Metabolism and Exercise
Energy
Source
Initial Amount
Enough for
ATP
Stored
3 mmoles
2 - 5 sec
CrP
Stored
20 mmoles
10 - 15 sec
Glycolysis
(anaerobic)
Aerobic
Via Stored
Glycogen
100 mmol
~ 130 sec
Via Stored
Glycogen and
contineous
supply of O2
and glucose
~ 40 min and
more
Prolonged activity is thus only possible by means of oxidative respiration and metabolism
(and a good supply of blood (for O2) and nutrients (via blood or internal glycogen stores)
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Energy Metabolism and Exercise
The higher our activity level, the
more ATP needed by the muscles
for contractile force production.
This is reflected in a higher Oxygen
consumption since O2 is used by the
mitochondria in the process of making
ATP (oxidative phosphorylation) !
O2 consumption
O2 demand and Exercise
Exercise Intensity
The more ATP needed, the more active the mitochondria, and the more
oxygen they require and consume.
When mitochondria cannot supply more ATP, we have reached the anaerobic
threshold (arrow); at that point more energy supply comes from anaerobic
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metabolism.
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Skeletal Muscle Types
Skeletal muscles can be classified into three broad groups
based on :
•  Speed of contraction (determined by speed of myosin ATPase
and speed of Ca++ pump ( relaxation)
•  Resistance to fatigue ( type of ATP supply)
Fast twitch glycolytic muscle fibers
Fast twitch oxidative muscle fibers
Slow twitch oxidative muscle fibers
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Skeletal Muscle Types
Speed of contraction is determined by the isoform of myosin ATPase !
The faster the ATPase splits ATP, the faster a cross bridge cycle
can be accomplished.
This translates into faster tension developments ! (the steeper the
upwards slope of the graph, the faster the tension developed ).
Fast twitch muscle fibers also
pump Ca2+ faster back into the
S.R., which thus indicates a faster
Ca2+ - pump as well.
This translates into shorter twitch
duration due to a faster relaxation.
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Skeletal Muscle Types
Slow twitch oxidative muscle fibers (also called Type I fibers
or red muscle fibers) rely on aerobic metabolism for ATP.
•  Contain many mitochondria
•  Contain good blood supply with dense capillaries
•  Contain myoglobin ( = muscle pigment that binds oxygen (similar to
hemoglobin in blood) which helps in the oxygen supply and
transport to the mitochondria.
•  Since they contract slowly and have good supply of oxygen, they
are fatigue resistant (don’t run out of ATP).
•  Examples : muscle used for maintaining posture,
standing
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Skeletal Muscle Types
Fast twitch glycolytic muscle (also called Type II-A fibers
or white muscle fibers) rely mostly on glycolysis for ATP.
•  They contain relatively few mitochondria.
•  They contain poor blood supply
•  They contain a good store of glycogen
•  Run out of ATP faster and produce lactic acid, resulting
in acidification
•  Fast glycolytic muscle thus fatigue easily.
•  Examples : biceps
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Skeletal Muscle Types
Fast twitch oxidative muscle fibers (also called Type II
B fibers or intermediate fibers) rely on glycolysis and
aerobic metabolism for ATP.
•  They are sort of an intermediate muscle
•  They resemble Type II A fibers in that they have little myoglobin
(pale looking muscles).
•  They resemble Type I fibers in that they have intermediate
mitochondrial density and capillaries.
•  They are thus intermediate with respect to fatigue as well.
•  Depending on exercise and training, they will gain more
mitochondria and more capillaries will supply these muscles
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Slow-oxidative skeletal muscle
responds well to repetitive
stimulation without becoming
fatigued; muscles of body posture
are examples.
Fast-oxidative skeletal muscle
responds quickly and to repetitive
stimulation without becoming
fatigued; muscles used in walking
are examples.
Fast-glycolytic skeletal muscle is
used for quick bursts ofstrong
activation, such as muscles used to
jump or to run a short sprint.
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Skeletal Muscle Types
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Skeletal Muscle and Fatigue
Origins of fatigue
•  Higher ATP demand compared to the capacity to
generate ATP… it depletes the ATP energy stores
(lack of CrP & glycogen also results in fatigue)
•  Accumulation of Pi due to breakdown of CrP
•  Accumulation of H+ due to breakdown of ATP and
production of lactic acid
•  Accumulation of K+ in the T-tubules, resulting in
Action Potential conduction failure
•  Synaptic fatigue : motor axon terminal runs out of ACh
•  Central Command fatigue : psychologically tired
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Myotonia Congenita
•  A genetic, neuromuscular channelopathy ( pathology
relating to an ion channel) that affects skeletal muscles
•  The hallmark of the disease is the failure of initiated
contraction to terminate, often referred to as delayed
relaxation of the muscles (myotonia) and rigidity.
•  The disorder is caused by mutations in part of a gene
(CLCN1) encoding the ClC-1 Chloride channel
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Myotonia Congenita
• 
During normal repeated action potentials, K+ tends to accumulate
in the T-tubules. The higher extracellular K would results in a
higher membrane potential ( see Nernst Equation).
•  The presence of chloride ion channels prevents this, as higher
membrane potentials result in more Chloride ions leaking inside,
negating the K+ effect.
• 
A higher activity in the Na/K pump ( pumping 2 K+ in fore 3 Na+
out) would also help in this membrane potential deficiency.
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Myotonia Congenita
K+ accumulates during repeated AP
Cl- movement
counteracts the
drift in RMP
Cl-
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Myotonia Congenita
• 
When the chlorine ion channel is
defective, the resting membrane
potential drifts upwards,
eventually reaching threshold,
and causing spontaneous muscle
AP’s in the absence of motor
neuron AP’s.
•  These spontaneous AP’s in the
muscle cell result in persistent
muscle contraction and delayed
relaxation after voluntary
movements.
The top graph shows AP recording in a myotonic goat, showing a few delayed
APs after stimulation and an increase in RMP ( dashed line).
The bottom graph shows a stronger stimulation, resulting in a RMB reaching
threshold, triggering a series of AP even after the stimulus is removed.
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Myotonia Congenita
Both humans (Thomsen and Becker myotonia) and animals ( like the fainting
goat) can be affected by this disease. It usually affects leg muscles and is
apparently painless and most often not lethal. Myotonia congenita has been
estimated to occur once in every 100,000 people worldwide
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