Biophysical basis for airway hyperresponsiveness

Steven S. An, Jeffrey J. Fredberg

Research output: Contribution to journalArticle

Abstract

Airway hyperresponsiveness is the excessive narrowing of the airway lumen caused by stimuli that would cause little or no narrowing in the normal individual. It is one of the cardinal features of asthma, but its mechanisms remain unexplained. In asthma, the key end-effector of acute airway narrowing is contraction of the airway smooth muscle cell that is driven by myosin motors exerting their mechanical effects within an integrated cytoskeletal scaffolding. In just the past few years, however, our understanding of the rules that govern muscle biophysics has dramatically changed, as has their classical relationship to airway mechanics. It has become well established, for example, that muscle length is equilibrated dynamically rather than statically, and that in a dynamic setting nonclassical features of muscle biophysics come to the forefront, including unanticipated interactions between the muscle and its time-varying load, as well as the ability of the muscle cell to adapt (remodel) its internal microstructure rapidly in response to its ever-changing mechanical environment. Here, we consider some of these emerging concepts and, in particular, focus on structural remodeling of the airway smooth muscle cell as it relates to excessive airway narrowing in asthma.

Original languageEnglish (US)
Pages (from-to)700-714
Number of pages15
JournalCanadian Journal of Physiology and Pharmacology
Volume85
Issue number7
DOIs
StatePublished - Jul 1 2007

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Keywords

  • Airway smooth muscle
  • Cytoskeleton
  • Malleability
  • Plasticity
  • Stiffness

ASJC Scopus subject areas

  • Physiology
  • Pharmacology
  • Physiology (medical)

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