SMOOTH MUSCLE MECHANISMS IN DYNAMIC AIRWAY PROPERTIES

Project: Research project

Description

Changes in airway tone which occur in response to changes in lung volume
play a significant role in the regulation of airway caliber. In previous
studies, we have demonstrated that many of the effects of lung volume
history on airway tone can be attributed to the hysteretic properties of
the airway smooth muscle itself. In addition, the mechanisms underlying
airway hysteresis appear to be caused primarily by active contractile
properties of the muscle. Some of these properties are affected by the
level of activation of the muscle and may be altered by factors which
affect intracellular Ca2+ homeostasis. The objectives of the proposed experiments are to determine the cellular
mechanisms underlying airway hysteresis, and to evaluate how they are
affected by modifications in Ca2+ homeostasis. To accomplish this goal we
will investigate the mechanisms by which the contraction of airway smooth
muscle is affected by muscle length and length history. We will also
investigate the mechanisms by which intracellular Ca2+ is regulated in
airway muscle, as these processes may ultimately determine the nature of
the mechanical responses of the tissue. A number of different techniques and approaches will be employed to
accomplish these objectives. Measurements of shortening velocity and of
muscle stiffness will be used to evaluate the effects of length history on
crossbridge properties. The effects of changes in muscle length or load on
the intracellular Ca2+ concentration will be determined using the
intracellular Ca2+ indicator, acequorin. Skinned muscles will be used to
assess the effects of Ca2+ activation. The mechanisms underlying Ca2+
homeostasis will be evaluated using aequorin, electrophysiologic
measurements, and pharmacologic interventions. The results of these studies should provide a better understanding of the
mechanisms responsible for airway hysteresis, and enable factors important
to the modification of airway hysteretic properties to be assessed. Numerous studies have demonstrated an abnormal hysteresis of the airways of
asthmatics, apparently caused by abnormalities in the properties of their
airway smooth muscle. These studies could therefore provide a basis for a
better understanding of mechanisms of asthma.
StatusFinished
Effective start/end date4/1/831/31/17

Funding

  • National Institutes of Health: $517,630.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $378,438.00
  • National Institutes of Health: $206,670.00
  • National Institutes of Health: $267,741.00
  • National Institutes of Health
  • National Institutes of Health: $270,717.00
  • National Institutes of Health
  • National Institutes of Health: $287,202.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $335,250.00
  • National Institutes of Health
  • National Institutes of Health: $377,500.00
  • National Institutes of Health: $335,250.00
  • National Institutes of Health
  • National Institutes of Health: $525,514.00
  • National Institutes of Health: $68,537.00
  • National Institutes of Health: $335,250.00
  • National Institutes of Health: $360,250.00
  • National Institutes of Health: $378,750.00
  • National Institutes of Health: $377,500.00
  • National Institutes of Health
  • National Institutes of Health: $390,000.00
  • National Institutes of Health: $377,500.00
  • National Institutes of Health: $382,200.00

Fingerprint

Smooth Muscle
Muscles
Respiration
Contractile Proteins
Integrins
Cytoskeletal Proteins
Homeostasis
Lung
Asthma
Proteins
Extracellular Matrix
History
Aequorin
Bronchoconstrictor Agents
Second Messenger Systems
Actin Cytoskeleton
Phosphorylation

ASJC

  • Medicine(all)