Regulation of Airway Smooth Muscle Contraction by Ca2+ Signaling: Physiology Revealed by Microscopy Studies of Lung Slices
Signaling…?>An examination of the physiology of airway smooth muscle cells (SMCs) in lung slices from mice, rats, and humans with laser scanning microscopy reveals that agonist-induced airway SMC contraction is driven by Ca2+ oscillations. An increase in the frequency of Ca2+ oscillations correlates with an increase in airway contraction. In addition, contractile agonists simultaneously increase airway SMC Ca2+ sensitivity to enhance the action of the Ca2+ oscillations. These Ca2+ oscillations are primarily mediated by the activity of the inositol trisphosphate receptor (IP3R). Although airway SMCs contract in response to membrane depolarization, Ca2+ influx via voltage-gated Ca2+ channels does not appear to have a major role in agonist-induced airway SMC contraction. Airway relaxation induced by β2-adrenergic receptor agonists involves both a reduction in the Ca2+ oscillation frequency and Ca2+ sensitivity.
KeywordsConfocal microscopy Inositol trisphosphate receptor Contraction Ca2+ oscillation frequency
This work was supported by National Institutes of Health Grant HL 103405. I would also like to thank Albrecht Bergner, Jose Perez-Zogbhi, Yan Bai, Philippe Delmotte, and Anna Ressmeyer, who conducted most of the experimental work addressed in this chapter.
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