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

Abstract

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.

• Authors: Michael J Sanderson, Philippe Delmotte, Yan Bai, Jose F Perez-Zogbhi
• Journal: Proceedings of the American Thoracic Society (Proc Am Thorac Soc) Vol. 5 Issue 1 Pg. 23-31 (Jan 01 2008) ISSN: 1546-3222 [Print] United States
• PMID: 18094081 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

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

Topics

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