BIOPHYSICS OF MUSCLE CONTRACTION

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BIOPHYSICS OF MUSCLE CONTRACTION

• Ivan Poliacek

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TYPES OF MUSCLES

• Skeletal muscle
• - striated muscle tissue existing under control
  of the somatic nervous system (voluntary
  control)
• Cardiac muscle
• - special striated muscle tissue of the heart
  working automatically and under the influence
  of autonomic nervous system (involuntarily)
• Smooth muscle
• - non-striated muscle tissue activated by
  autonomic nervous system, hormones, or simply
  stretching

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• Surrounds each bundle

cell
Surrounds each cell
Fascia Becomes the muscle sheath which fuses with
the tendon
Bundles of collagen fibers
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• Deep structures of a sceletal muscle

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Muscle fiber muscle cell

• The sarcolemma the cell membrane (plasma
  membrane) of a muscle cell
• - conduct stimuli
• - an outer coat (thin layer of polysaccharides
  with collagen fibrils) that fuses with a tendon
  fiber (they collect into bundles to form the
  muscle tendons)
• Sarcoplasm - cytoplasm with organelles
• Myofibrils - cylindrical organelles
• contractive elements the actin and myosin
  filaments (the length a few µm)
• organized in repeated subunits along the
  length of the myofibril - sarcomeres
• Sarcoplasmic reticulum with T- tubules internal
• conductive system

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• Structure
• of
• a muscle
• cell

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• A microscopic photo and a scheme of

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a maximum contraction of sarcomere is about 30
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• Skeletal muscle
• attached to the bones for movement
• several types of fibers (speed, stamina, fatique,
  force, motor unit size, structure...)
• cells - long multi-nucleated cylinders - the
  length of muscle cell is a few mm (human sceletal
  muscle), the diameter is typically 100 - 150 µm
• cytoskeleton supporting the cell shape

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Summary 1

• What is basic and deep structure of skeleton
  muscle?
• What is the sctructure of muscle cell (fiber)?
  How does this cell look like?
• What is the endomysium among the muscle cells
  for?
• What organel is responsible for contraction how
  is it arranged?
• What are contractille elements molecules?
• How is contraction performed?

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What does drive the muscle?What is making the
muscle to contract?
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Motor fibers (axons of motoneurons) within the
motor nerves conduct action potentials to the
neuro-muscular junction - end-plate.
Action potential at the pre-synaptic membrane -
activates voltage-gated Ca channels - Ca2
influx - vesicles with neurotransmitter
Acetylcholine (ACh) release acetylcholin into the
synaptic cleft
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acetylcholine
Acetylcholin binds with nicotinic receptors on
postsynaptic membrane of muscle cell (motor
end-plate) activation of Na channels
depolarization EPSP end plate potential

• acetylcholine is eliminated by breaking down with
  the acetyl cholinesterase

nicotinic ACh receptor
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Intracellular recordingfrom a muscle fiber

• A nerve impulse reaching
• the axon terminal releases
• ACh into the neuromuscular
• junction.
• ACh produces EPSP
• end plate potential (EPP)
• in the membrane beneath
• the terminal (the subsynaptic
• end-plate membrane) (A
• in the graph), but not farther
• away (B).
• When the EPP reaches
• the threshold (about -50 mv),
• an action potential is
• generated that sweeps
• along the fiber (A to B
• in the graph).

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• If a single vesicle occasionally release ACh into
  the synaptic cleft the miniature EPSP (miniature
  end-plate potential) is produced NO ACTION
  POTENTIAL follows
• Full EPSP full end-plate potential - EPP (due to
  synaptic action AP Ca2 influx - many
  vesicles release) always reaches the firing level
  and produces action potential at the muscle cell.
• Action potential spreads along the sarcolemma and
  via T- tubules of the muscle cell depolarizes the
  terminal cisternae and the sarcoplasmatic
  reticulum.

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Motor unit

• Connective tissue separates muscle cells - each
  one must be stimulated by a motoneuron
• Motor unit - all muscle cells innervated by the
  same motoneuron they will contract at the same
  time
• Motor units vary in size - mostly mixture of
  motor units of different sizes
• large motor units gt100 cells (typically slow
  postural muscles)
• small motor units about 10 cells (precise
  control fast acting muscles
• those moving the eye)

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Recruitment of motor units
Increasing level of central (moto-neuronal)
activation successive activation of higher
threshold motor units
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Summary 2

• Where is the signal activating skeleton muscle
  coming from?
• Where is it transmitted to the muscle?
• What is the function of Ca?
• What is the name for EPSP at the muscle cell?
• What receptors and what mediator are involved in
  synaptic transmission from the motoneuron to the
  muscle cell?
• What is the course of action potential at the
  muscle fiber?
• How far (where) the action potential at the
  muscle cell travel?
• How many muscle cells are supplied with single
  motoneuron?
• Can nearby muscle fibers be activated
  differently?
• When and how much are all muscle fibers
  activated?

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The shape and some parameters of muscle fiber
action potential
the rest
intracellular
extracellular
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Extracellular recording of parasternal muscle EMG
2 different motor units are present
200 µV
10 ms
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The mechanism.What happens on the way from
action potential to the contraction of the muscle?
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• The sarcoplasmic reticulum surrounds the
  myofibrils and holds
• a reserve of the Ca2 ions. A transverse T -
  tubules are the pathway
• for the action potential to signal the
  sarcoplasmic reticulum.

Action potential on T-tubules - depolarizes
sarcoplasmic reticulum - activates voltage-gated
Ca channels - Ca2 released into intracellular
space of muscle fiber Ca2 initiates muscle
contraction
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Muscle contraction is provided by interaction of
ACTIN (thin) and MYOSIN (thick) fibers
(filaments). Tropomyosin covers binding spots of
actin at a rest state.
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Muscle contracts when myosin heads make a
cross-bridges (bonds) with actin and the heads
bend pulling the actin filament deeper among the
myosin filaments.
the cycle bind bend release 1 stroke
10-12 nm
As far as Ca2 and ATP is present (around the
Actin and Myosin) the cycle binding, bending,
releasing and straightening of myosin heads
continue (contraction). Ca2 is constantly
pumped (by a Ca pump) back into the sarcoplasmic
reticulum ( extracellular space, tubules,
cisternae). In order to keep high Ca2
concentration - further action potentials has to
release it again and again. Without Ca2
tropomyosin returns back (conformation) over
actin filament blocking its binding loci stop
contraction.
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Crossbridge binding Scheme of chicken muscle
myosin head. The movement is likely much more
distributed including the movement at the
actin-myosin interface. (Rayment et al. Science
261 50-58, 1993)
Each myosin molecule contains two peptide heavy
chains which are cleaved enzymatically to produce
a myosin tail and two globular heads or
crossbridges. The crossbridge heavy chain has
a tail region (shown in blue)
around which two smaller peptides wrap.
These peptides are the light chains
(yellow and red) which stabilize, and in
some cases, regulate the myosin.
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Myosin filament with myosin heads each 14.5 nm.
294 myosin molecules on the thick filament (588
ATP-ase binding spots).
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Ca2 binds with troponin, changes shape
(conformation) of tropomyosin that exposes the
actin binding spots on actin filament. The
muscle contraction requires the ATP.
As the ATP is required to release the actin
myosin binding without ATP RIGOR MORTIS.
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For the unbinding the myosin head from the
actinand its straightening, the ATP is
required. Myosin hydrolyze ATP (lyse it into
ADP and phosphate) gathering the energy
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Summary 3

• What is sarcoplasmic reticulum for?
• What happens when sarcoplasmic reticulum membrane
  is depolarized?
• What is the function of Ca?
• What happens when the Ca is pumped back to the
  reticulum and other areas out of muscle cell
  intracellular space?
• How tropomyosin affect the muscle cell
  contraction?
• What is the role of ATP in muscle contraction?
• What happens when there is no ATP in the muscle
  cell?
• Why the sequence actin myosin connection
  bending myosin heads (pulling the actin
  molecules) release and stretch of myosin heads
  occur?
• For what exactly is the ATP energy used?

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Single muscle twitch

• Increased intracellular Ca2 concentrations (Ca2
  released from sarcoplasmic reticulum and T
  tubules) lasts longer than action potentials
• even longer lasts single muscle twitch

- no action potential from other than related
motoneuron - SUMMATION is TEMPORAL at the level
of Ca2 release and twitches overlapping
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Single muscle twitch unfused fused tetanus

• A tetanic contraction - motor unit stimulated by
  a high frequency
• of action potentials from its motoneuron
• The time between stimuli is shorter than single
  twitch durations no time to relax -
  superposition of muscle twitches and (temporal)
  summation of contraction
• The strength of contractions increases
• - it is added to the previous twitch

Incomplete (unfused) tetanus
Complete (fused) tetanus
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The opposite acting muscle to the agonist is the
antagonist (e.g. flexing the elbow biceps brachii
- agonist, the triceps brachii - antagonist)
An antagonist is never totally relaxed -
control and damping of movement by maintaining
tone against the agonist (eccentric movement)
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Summary 4

• What is the duration of the action potential,
  increased Ca intracellular concentration, and
  single muscle twitch?
• What type of summation works for muscle
  contraction?
• How many motoneurons can stimulate the particular
  muscle cell?
• Compare the frequencies of activation of a muscle
  cell during unfused and fused tetanus?
• How is maximum contraction of the muscle cell
  achieved?
• How are working oppositely connected muscles?

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Summary of muscle contraction
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• Short rest
• The time for thinking and organizing infos.

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MUSCLE PROPERTIES

• Elasticity or recoil
• - muscles have elastic elements which cause
  them to recoil to their original size.
• Stretchability or extensibility
• - muscles can also stretch and extend to a
  longer- than-resting length
• Excitability and responsiveness
• - muscle tissue can be stimulated by
  electrical, physical, or chemical means
• Contractility transformation of chemical energy
  into the mechanical work - movement
• - the response of muscle tissue to stimulation
  is contraction, or shortening
• muscles can only pull, they cannot push

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Smooth muscle

• Visceral (smooth) muscle
• - in the body's internal organs and blood
  vessels
• - no striations
• - layers in the mucous membranes of the
  respiratory and digestive systems, bands in the
  walls of blood vessels, and sphincter muscles.
• Smooth muscle fibers - a fusiform shape - a
  spindle-like shape (wide in the middle and tapers
  at both ends) - 20-500 µm in length.
• The ratio of actin to myosin is 6 1 in
  skeletal muscle, 4 1 in cardiac muscle and
  16.5 1 in smooth muscle.
• Greater elasticity and ability to stretch and
  still maintain contractility than striated
  muscle.

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Intestine smooth muscle
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Smooth muscle contraction

• Contraction - sliding of myosin and actin
  filaments - hormones, neurotransmitters, drugs,
  etc.
• Single unit smooth muscle tissue is connected
  into a syncytium - the autonomic nervous system
  innervates a single cell within a sheet or bundle
  - the action
• potential
• propagates
• by gap junctions
• to neighboring
• cells (all
• contract together).
• Smooth muscle may contract spontaneously
• - it is myogenic (via ion channel dynamics or
  pacemaker cells - interstitial cells of Cajal in
• the gastrointestinal tract).

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Smooth muscle contraction
Multiunit smooth muscle tissues - individual
cells are innervated by the autonomic nervous
system (fine control and gradual responses, much
like in skeletal muscle) - the trachea, the
elastic arteries, the iris of the eye). No
troponin, but instead calmodulin is regulatory
protein in smooth muscle, also tropomyosin
doesn't serve the regulatory function as in
striated muscle. Contraction is initiated by a
Ca-regulated phosphorylation of myosin, rather
than a Ca-activated troponin system. Smooth
muscle thin filaments mainly actin,
tropomyosin, and caldesmon.
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Summary 5

• What is elasticity, stretchability, excitability,
  and contractiliry?
• What are main differences between skeletal and
  smooth muscles?
• What does it mean syncytium?
• What does it mean myogenic activity?
• What is the molecule the Ca interact with in
  the smooth muscle vell instead of troponin of
  skeleton muscle cell?
• How is contraction of multiunit smooth muscle
  cell initiated?

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Heart muscle

• Cardiac muscle
• - much shorter cells than skeletal muscle
• - cardiac muscle cells connect to one another
• - gap junctions - intercalated discs -
  electrochemical impulse can pass to all
  connected cells - syncytium (the cells work as
  a unit)

Faint striations - similar, but not identical,
arrangement of myofilaments in cardiac and
skeletal muscle Many cardiac muscle cells are
myogenic activation arises in the heart not
from the nervous system - heart natural rhythm
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• A scheme of intercalated discs of cardiac muscle

cytosol
connexin proteines
gap junctions create cytoplasmic bridges
intercellular space
cell membrane

• In cardiac myocytes, influx of Na trigger
  calcium-induced calcium release - Ca2 influx
  through voltage-gated calcium channels on the
  sarcolemma leading to the release of Ca2 from
  the sarcoplasmic reticulum

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and its relation to the ECG waveform
Long-lasting action potential - long refractory
period - no temporal summation - no tetanic
contraction
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Relation of electrical and mechanical
characteristics of heart action
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Spreading of electrical (action potential)
activity from the sinoatrial node to the tissue
of heart atria atrioventricular node and
then into the ventricular heart tissue with the
recording of the related ECG waveform.
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Summary 6

• What is function of intercalated discs?
• How are cardio-myocytes activated?
• What is calcium induced calcium release?
• What is the consequence of it?
• How much longer is cardio-myocyte action
  potential than neuron action potential?

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A comparison of the properties of skeletal,
cardiac, and visceral muscle
 Property  SkeletalMuscle  CardiacMuscle  SmoothMuscle
 Striations?  Yes Yes  No
 Relative Speed of Contraction Fast   Intermediate  Slow
 Voluntary Control? Yes  No No
 MembraneRefractory Period  Short  Long  
 Nuclei per Cell  Many  Single  Single
 Control of Contraction  Nerves  Beats spontaneouslybut modulated by nerves  NervesHormonesStretch
 Cells Connected byIntercalated Discs or Gap Junctions?  No  Yes  Yes