Regulation of airway smooth muscle cell contractility by Ca2+ signaling and sensitivity

Proc Am Thorac Soc. 2008 Jan 1;5(1):23-31. doi: 10.1513/pats.200704-050VS.


Airway smooth muscle cell contraction is regulated by changes in intracellular Ca2+ concentration ([Ca2+]i) and the responsiveness of the airway smooth muscle cell to this Ca2+. The mechanism controlling [Ca2+]i primarily involves agonist-induced release of Ca2+ from internal stores to generate Ca2+ oscillations. The extent of contraction correlates with the persistence and frequency of these Ca2+ oscillations. The maintenance of the Ca2+ oscillations requires Ca2+ influx, but membrane depolarization appears to have a minor role in initiating or sustaining contraction. Contraction also requires agonist-induced Ca2+ sensitization, which is mediated mainly by decreases in myosin light-chain phosphatase activity. Although it is not clear if airway hyperresponsiveness associated with asthma results from the specific modulation of these Ca2+-based regulatory mechanisms, bronchodilators relax airways by both attenuating the Ca2+ oscillations and by decreasing the Ca2+ sensitivity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Asthma / physiopathology*
  • Calcium Channels / physiology
  • Calcium Signaling / drug effects
  • Calcium Signaling / physiology*
  • Humans
  • Inositol 1,4,5-Trisphosphate Receptors / physiology*
  • Membrane Potentials
  • Muscle Contraction / drug effects
  • Muscle Contraction / physiology*
  • Muscle Relaxation / drug effects
  • Muscle Relaxation / physiology*
  • Muscle, Smooth / metabolism*
  • Ryanodine Receptor Calcium Release Channel / physiology*


  • Calcium Channels
  • Inositol 1,4,5-Trisphosphate Receptors
  • Ryanodine Receptor Calcium Release Channel