Wed 2/16 – Review and Q&A Session

Mon 2/21 – Midterm 1

Study guide is on Canvas

Final Exam: 5/10, 2:30-5, CKB 204

 BIOL 340 Mammalian Physiology Lecture 8
7

Muscles and Muscle Tissue

Midterm 1

Part 2 of 2
Contractions and Metabolism
 Muscle tension and contraction
• Relaxed, soft muscle
tissue can change into
hard elastic tissue within
milliseconds
• The force exerted by a
contracting muscle is
called muscle tension, the
opposing force is called
the load
• Muscles contract with
varying force for different
amounts of time,
depending on behavioral
context
 Muscle tension and contraction
• Contraction: generation of Isotonic Isometric
tension (force)
• Contraction increases movement
or tension: contraction does not
necessarily cause shortening of
the fiber
• Shortening occurs when tension
generated by cross bridges on
the thin filaments exceeds forces
opposing shortening
• Isotonic: tension > load 
shortening with constant tension
• Isometric: tension < load 
tension without shortening
 Muscle tension and contraction
Isotonic contractions:
• Concentric
• Muscle shortens and
does work
• Eccentric
• Muscle generates force
while it lengthens
(important for
coordination and
purposeful movements)
 Muscle tension and contraction
Isometric
Myogram
• Tension can be recorded with a
force transducer while the
muscle length is not changing
 Muscle tension and contraction
Twitch contraction (response to single stimulus)
Myogram
• Latent period
It takes a few milliseconds for the
electrical response and the excitation-to-
contraction coupling to take effect, until
cross bridge cycling produces appreciable
contraction.
• Period of contraction
10-100 ms of active cross bridge cycling
while Ca2+ is high, from onset to peak
tension.
• Period of relaxation
Ca2+ is being pumped back into the SR,
inhibiting cross bridge cycling. Relaxation
is slower than contraction (important for
temporal summation).
 Muscle tension and contraction
Twitch contractions in 3 different muscles

• Contraction kinetics can differ

substantially across muscles.
• Differences are due to
differences in enzymes,
metabolic properties, myofibrils.
• Differences are important for
graded contractions (temporal
summation).
Muscle tension and contraction
Graded contractions
• We don’t produce movement with
twitch contractions.
• Our movements are smooth.
• We have precise control over speed,
force, and range of contractions.
 Muscle tension and contraction

Individual twitches Temporal summation Temporal summation

• Contraction dynamics is much slower
than electrical responses, and
relaxation is slower than contraction.
• With increasing stimulus frequency
(when a motor neuron fires
Unfused tetanus Fused tetanus repeatedly), tension summates across
consecutive stimuli.
• Tension peaks eventually reach a
dynamic steady state (unfused
tetanus).
• At even higher frequencies of
stimulation, tension peaks fuse
completely, producing smooth
responses.
Muscle tension and contraction
Force production

• Force production in our muscles

operates over a wide range.
• We produce smooth
movements over that range of
force, even when using the
same muscles.
Muscle tension and contraction
The motor unit
• Muscles can be innervated by
hundreds of motor neurons.
• Each muscle fiber is innervated
by only one α-motor neuron
• Each motor neuron innervates
multiple fibers
 Muscle tension and contraction
The motor unit
• Muscles can be innervated by
hundreds of motor neurons.
• Each muscle fiber is innervated
by only one α-motor neuron
• Each motor neuron innervates
multiple fibers

Motor unit: 1 α-motor neuron + all muscle fibers it innervates

 Muscle tension and contraction
Stimulation experiment Recruitment

• Increasing force requirements

are responded to in two ways:
• A single motor neuron can
increase firing frequency to
produce more tension in the
fibers it innervates.
• The number of activated motor
neurons (and therefore motor
units) can increase.
 Muscle tension and contraction
Recruitment
Voluntary force production

• Increasing force requirements

are responded to in two ways:
• A single motor neuron can
increase firing frequency to
produce more tension in the
fibers it innervates.
• The number of activated motor
neurons (and therefore motor
units) can increase.
 Muscle tension and contraction
Sequential activation of motor
units is not random, but is
following the size principle:
• Smaller motor neurons are
activating smaller fibers
• Smaller motor neurons are
activated first (higher
resistance  less synaptic current
needed to change membrane
potential: V = I * R)
• Successive recruitment does
not increase tension
linearly, but later activated
units increase tension more
 Muscle tension and contraction
Different fiber sizes and
recruitment thresholds are also
associated with different
metabolic properties:
• Small fibers build up tension
slowly and do not show fatigue
(control of posture)
• Intermediate fibers build up
tension fast and do not fatigue
easily (important for repeated
motor activity like walking)
• Large fibers are fast, produce the
most force, but are rapidly
fatigued (short bursts of high
activity, like in jumping)
 Muscle metabolism
• ATP is the only energy source used directly for
contractile activities:
• Move and detach cross bridges

1
4 2
3
 Muscle metabolism
• ATP is the only energy source used directly for
contractile activities:
• Move and detach cross bridges
• Ca2+ pumps in SR membrane
1
4 2
3
Muscle metabolism
• ATP is the only energy source used directly for
contractile activities:
• Move and detach cross bridges
• Ca2+ pumps in SR membrane
• Return of Na+ and K + after excitation-
contraction coupling (Na+/K+ pump)
• Problem: muscle cells do not store a lot of ATP
(depleted in 4–6 seconds)
• Three ways to replenish ATP:
• Direct phosphorylation of ADP by creatine
phosphate (CP)
• Anaerobic pathway (glycolysis  lactic acid)
• Aerobic respiration
 Muscle metabolism
Direct phosphorylation
• Muscles store 2-3 times more creatine
phosphate than ATP
• Fast and readily reversible reaction
• No O2 required
• Together, stored ATP and CP provide
energy for about 15s
 Muscle metabolism
Anaerobic pathway
• ATP from glycolysis in cytosol (does not
require O2).
• Fueled by glucose from glycogen in
blood and muscle stores (glycosomes!)
• Fast but inefficient (2 ATP per glucose)
• Useful when blood flow is impaired
during strenuous exercise (bulging
muscles compress blood vessels)
• Produces lactic acid (metabolized
elsewhere, partly responsible for
soreness)
• Can provide energy for 30-40s
 Muscle metabolism
Aerobic pathway
• Produces 95% of ATP during rest and
light to moderate exercise; slow
• Series of chemical reactions that require
O2 (myoglobin in muscle!) and occur in
mitochondria
• Breaks glucose into CO2, H2O, and large
amount ATP (32 per glucose compared
to 2 in anaerobic pathway)
• Fuels - stored glycogen, then bloodborne
glucose, pyruvic acid from glycolysis,
and free fatty acids and amino acids
• Provides energy for hours
Muscle metabolism
 Muscle metabolism
Muscle fatigue
• Ionic imbalance: excessive K+ efflux reduces electrical responses
• Increased Pi from CP and ATP breakdown interferes with Ca2+ release
and myosin dephosphorylation
• Decreased [ATP] leads to more unbound Mg2+, which affects L-type
Ca2+ channels
• Decreased glycogen
Recovery
• Must replenish O2 stored in myoglobin (“panting”)
• Must remove lactic acid (reconvert to pyruvic acid)
• Must replace glycogen stores
• Must resynthesize ATP and CP
 Anaerobic exercise incurs an “O2 debt”, called the excess postexercise
O2 consumption (EPOC)
 Muscle metabolism
  Slow oxidative fibers Fast oxidative fibers Fast glycolytic fibers
Contraction speed Slow Fast Fast
fast fatigable Cross bridge cycle Slow Fast Fast

Primary ATP synthesis Aerobic Aerobic (some glycolysis) Anaerobic glycolysis

Myoglobin High High Low
fast fatigue-resistant
Stored glycogen Low Intermediate High
Recruitment First Second Third
Fatigue Resistant Moderately resistant fatigable

slow short powerful

Activities suited for Endurance, posture walking, running
movements

Large (humans), Large,

Fiber diameter Small
intermediate intermediate (humans)

Mitochondria Many Many Few

Capillaries Many Many Few
Appearance Red (“red meat”) Red to Pink Pale (“white meat”)
 Summary
• Muscle tension (force) builds up during cross bridge cycling, either causing length change
when resistance (load) is overcome by tension (isotonic contraction) or causing just muscle
tone when it doesn’t (isometric contraction).
• Tension responses to single action potentials are much slower than the underlying electrical
events, and differ in time course between different muscles.
• The slow time course facilitates temporal summation across repetitive input, leading to a
tension plateau after several inputs (tetanus). This allows for smooth contraction responses.
• Increasing force requirements are met by 1) increase in motor neuron firing frequency, and 2)
successive recruitment of more and more motor units.
• Sequential activation of motor units is not random, but is by class of fiber that differ in size,
force production, and susceptibility to fatigue (resulting from structural and biochemical
differences).
• Muscle fibers can use three different ways to replenish ATP: 1) direct phosphorylation from
creatine phosphate, 2) fast anaerobic [O2-independent] glycolysis, 3) slow aerobic glycolysis.
REVIEW QUESTIONS
• Why are eccentric contractions useful?
• Why is it useful that the time course of
contractions is longer than that of the motor
neuron action potential?
• What is a motor unit?
• What is the size principle?
• In the long run, why isn’t the anaerobic pathway
truly independent of O2?