Journal
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
Volume 297, Issue 2, Pages L347-L361Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajplung.90559.2008
Keywords
lung slices; Ca2+-induced Ca2+ release; membrane depolarization; tetracaine
Categories
Funding
- National Heart, Lung, and Blood Institute [HL-71930, HL-087401]
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Bai Y, Edelmann M, Sanderson MJ. The contribution of inositol 1,4,5-trisphosphate and ryanodine receptors to agonist-induced Ca2+ signaling of airway smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 297: L347-L361, 2009. First published May 22, 2009; doi:10.1152/ajplung.90559.2008.-The relative contribution of inositol 1,4,5-trisphosphate (IP3) receptors (IP(3)Rs) and ryanodine receptors (RyRs) to agonist-induced Ca2+ signaling in mouse airway smooth muscle cells (SMCs) was investigated in lung slices with phase-contrast or laser scanning microscopy. At room temperature (RT), methacholine (MCh) or 5-hydroxytryptamine (5-HT) induced Ca2+ oscillations and an associated contraction in small airway SMCs. The subsequent exposure to an IP3R antagonist, 2-aminoethoxydiphenyl borate (2-APB), inhibited the Ca2+ oscillations and induced airway relaxation in a concentration-dependent manner. 2-APB also inhibited Ca2+ waves generated by the photolytic release of IP3. However, the RyR antagonist ryanodine had no significant effect, at any concentration, on airway contraction or agonist-or IP3-induced Ca2+ oscillations or Ca2+ wave propagation. By contrast, a second RyR antagonist, tetracaine, relaxed agonist-contracted airways and inhibited agonist-induced Ca2+ oscillations in a concentration-dependent manner. ;However, tetracaine did not affect IP3-induced Ca2+ release or wave propagation nor the Ca2+ content of SMC Ca2+ stores as evaluated by Ca2+-release induced by caffeine. Conversely, both ryanodine and tetracaine completely blocked agonist-independent slow Ca2+ oscillations induced by KCl. The inhibitory effects of 2-APB and absence of an effect of ryanodine on MCh-induced airway contraction or Ca2+ oscillations of SMCs were also observed at 37 degrees C. In Ca2+-permeable SMCs, tetracaine inhibited agonist-induced contraction without affecting intracellular Ca2+ levels indicating that relaxation also resulted from a reduction in Ca2+ sensitivity. These results indicate that agonist-induced Ca2+ oscillations in mouse small airway SMCs are primary mediated via IP(3)Rs and that tetracaine induces relaxation by both decreasing Ca2+ sensitivity and inhibiting agonist-induced Ca2+ oscillations via an IP3-dependent mechanism.
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