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In vitro Measurements of Tracheal Constriction Using Mice
10:20

In vitro Measurements of Tracheal Constriction Using Mice

Published on: June 25, 2012

Calcium sensitization produced by G protein activation in airway smooth muscle

H Yoshimura1, K A Jones, W J Perkins

  • 1Department of Anesthesiology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.

American Journal of Physiology. Lung Cellular and Molecular Physiology
|August 16, 2001
PubMed

Insights

G protein activation influences airway smooth muscle force. Chronic G protein activation, unlike acute, increases maximal force through mechanisms beyond myosin light chain phosphorylation, impacting calcium sensitivity.

Area of Science:

  • Physiology
  • Biochemistry
  • Pharmacology

Background:

  • Smooth muscle contraction is regulated by intracellular calcium and myosin light chain (MLC) phosphorylation.
  • G protein-coupled receptors play a crucial role in modulating smooth muscle function.
  • Understanding the precise mechanisms of G protein signaling in smooth muscle is vital for therapeutic development.

Purpose of the Study:

  • To investigate if G protein activation affects smooth muscle force independent of regulatory myosin light chain (rMLC) phosphorylation.
  • To differentiate the effects of acute versus chronic G protein activation on airway smooth muscle contractility.
  • To elucidate the role of calcium (Ca2+) in G protein-mediated force generation.

Main Methods:

  • Utilized alpha-toxin-permeabilized canine tracheal smooth muscle preparations.
  • Measured force development in response to varying intracellular Ca2+ concentrations.
  • Administered acetylcholine (ACh), endothelin-1 (ET-1), or aluminum fluoride (AlF) for acute or chronic (1-h) exposure.
  • Employed thiophosphorylation of rMLC to assess its role in force generation.

Main Results:

  • Acute exposure to ACh, ET-1, or AlF enhanced Ca2+ sensitivity without altering maximal force.
  • Chronic AlF exposure, but not chronic ACh or ET-1, increased maximal force.
  • Chronic AlF-induced force increase was dependent on Ca2+ presence during activation and involved mechanisms independent of rMLC phosphorylation.

Conclusions:

  • Acute G protein activation primarily increases airway smooth muscle Ca2+ sensitivity via rMLC phosphorylation.
  • Chronic direct G protein activation can augment maximal force through Ca2+-dependent mechanisms independent of rMLC phosphorylation.
  • These findings reveal distinct pathways for acute and chronic G protein signaling in airway smooth muscle contractility.

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