Smooth muscle

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Smooth muscle

• Chapter 9
• pages 279 - 287

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Structure of smooth muscle

• Line many hollow organs and tubes in the body to
  control fluid flow and absorptive processes
• Also function to control iris diameter and
  stiffness of bones in middle ear that transmit
  sound into cochlea
• Smooth muscle myocytes are mononucleate and
  smaller (2 10 mm diameter) than skeletal muscle
  myocytes, length 50-400 mm vs. 10s of cm for
  skeletal
• Have thin actin and thick myosin filaments for
  contraction like skeletal muscle

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Structure of smooth muscle

• Unlike skeletal muscle, actin and myosin
  filaments are not organized in striated fashion
• Thin filaments are anchored to plasma membranes
  in protein structures known as dense bodies
• Reason for difference smooth muscle can
  maintain near-maximal tension levels over a
  larger range of contraction lengths
• This allows for normal function over wide range
  of tube volumes
• Example if your bladder had skeletal muscle,
  you may not be able to urinate when it is full!

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At what length do smooth muscles generate the
most force?

1. Partially contracted
2. Relaxed
3. Partially stretched
4. All of the above
5. None of the above

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Mechanisms of smooth muscle contraction

• Two significant differences between smooth and
  skeletal muscle contractions
• Cross-bridge cycling and sources of cytosolic
  Ca2
• Smooth muscle myosin has very slow ATPase
  activity
• Up to 100 times slower than skeletal muscle
  myosin ATPase
• This slow ATPase activity allows for maintenance
  of tension over long periods with very low ATP
  consumption to prevent fatigue
• Faster contractions require assistance of
  external ATPase

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Mechanisms of smooth muscle contraction

• Increase in cytosolic Ca2 leads to activation of
  protein calmodulin
• Activated calmodulin binds to myosin light chain
  kinase which serves as ATPase and phosphorylates
  myosin to energize it
• Constitutively active myosin light chain
  phosphatase continuously dephosphorylates myosin
  to allow for cycling and relaxation
• Tension levels determine by relative levels of
  myosin light chain kinase and phosphatase activity

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Activation of Smooth Muscle Contraction by
Calcium Ions
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Pathways Leading from Increased Ca2 to
Cross-Bridge Cycling
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Which step of the cross bridge cycle differs
between skeletal and smooth muscle?

1. Hydrolysis of ATP
2. Binding to actin
3. Release of actin and Pi
4. Binding of another ATP

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Sources of cytosolic Ca2

• Influx of extracellular Ca2 through
  voltage-gated Ca2 channels initiates contraction
• Smooth muscle has SR for Ca2-induced Ca2
  release (CICR)
• However, no specific pattern of SR around
  actin-myosin complexes
• No transverse tubules for excitation-contraction
  coupling
• Since smooth muscle fibers are smaller, Ca2
  influx through voltage-gated Ca2 channels gives
  larger rise in intracellular Ca2 levels

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Sources of cytosolic Ca2

• Ability to recruit SR gives finer control of
  muscle tension to individual fiber, known as
  graded contractions
• Skeletal muscle control due to recruiting
  additional fibers, not in the tension of
  individual fibers
• Ca2 release from SR does not require CICR, can
  also occur due to chemical signaling and second
  messenger production
• Ca2 clearance from cytoplasm is much slower,
  producing a single twitch that can last several
  seconds

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Initiation of smooth muscle contractions

• Unlike skeletal muscle, does not require direct
  innervation from presynaptic neuron
• Some smooth muscle fibers exhibit periodic
  contractions due to spontaneous depolarization
  known as pacemaker potential
• Lead to spontaneous APs in absence of external
  input
• Produced by constitutively active K and Ca2
  channels
• PCa/PK produces resting Vm above AP threshold
• Pacemaker potentials are common in digestive
  system
• Also found in some cardiac muscle fibers to
  produce heartbeat
• Some neurons also exhibit pacemaker potentials

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Generation of Aps in Smooth Muscle Fibers
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Modulation of smooth muscle contractions

• Nerve terminals present in smooth muscle function
  to modulate (increase or decrease) strength of
  contraction
• Tight coupling between presynaptic nerve terminal
  and smooth muscle fibers not required for smooth
  muscle contraction
• Single nerve terminal can activate numerous
  smooth muscle fibers
• Single smooth muscle fiber can respond to
  numerous nerve terminals
• Hormones diffusing from distal locations can also
  modulate smooth muscle

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Innervation of Smooth Muscle by a Postganglionic
Autonomic Neuron
Sympathetic or Parasympathetic
Neurotransmitters from from varicosities along
the branched neuron diffuses to receptors on
muscle cell plasma membranes
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Modulation of smooth muscle contractions

• Modulatory effects of neurotransmitters and
  hormones are generally due to the activation of
  GPCRs that alter intracellular Ca2 levels
• Example norepinephrine acts at a-adrenergic
  receptors to contract blood vessels
• Example norepinephrine acts at b-adrenergic
  receptors to relax bronchioles in lung
• Local agents such as acidity, O2 concentration
  and paracrine agents can modulate contractility
• Some smooth muscle fibers have mechanosensitive
  ion channels that produce contraction in response
  to stretch

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What is the relationship between the nervous
system and smooth muscle fibers?

1. Nervous system initiates contractions
2. Nervous system modulates contractions
3. No connection between nervous system and smooth
   muscle

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Gap junctions

• Many smooth muscle fibers are interconnected via
  gap junctions
• Single unit smooth muscle many gap junctions to
  act in coordinated fashion
• Leads to propagation of depolarizing stimuli to
  produce coordinated contractions
• Depolarizing stimuli propagated from specialized
  myocytes that serve as intrinsic pacemaker
• Prominent in heart and digestive system
• Multiunit smooth muscle few gap junctions to
  have independent activity
• Prominent in skin for motility of hairs
• Most smooth muscle incorporates both single and
  multiunit fibers

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Innervation of a Single Unit Smooth Muscle
is Often Restricted to Only a Few Cells in the
Muscle. Electrical Activity is Conducted From
Cell to Cell by Way of the Gap Junctions Between
the Muscle Cells
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Pacemaker Cells with a Slow Wave Pattern
Drift Periodically Toward Threshold Excitatory
Stimuli Can Depolarize the Cell to Reach
Threshold and Fire APs
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Summary of muscle types
Skeletal Smooth (single unit) Smooth (multiunit) Cardiac
Actin myosin Yes Yes Yes Yes
Striated sarcomeres Yes No No Yes
Transverse tubules Yes No No Yes
Gap junctions No Yes Few Yes
Source of Ca2 SR only SR Ca2 channels SR Ca2 channels SR Ca2 channels
Coupling to Ca2 Troponin Calmodulin-myosin Calmodulin-myosin Troponin
Contraction speed Fast Very slow Very slow Slow
Pacemaking No Yes Yes Yes in some
Muscle tone No Yes No No
Nerve stimulation Excitatory ( only) Modulatory (/-) Modulatory (/-) Modulatory (/-)
Hormone actions No Yes Yes Yes
Effects of stretch None Contraction None None
Maximal tension Relaxed length Wide length range Wide length range Stretched