The contribution of inositol 1,4,5-trisphosphate and ryanodine receptors to agonist-induced Ca2+ signaling of airway smooth muscle cells
| Autor: | Yan Bai, Martin Edelmann, Michael J. Sanderson |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Boron Compounds
Male Pulmonary and Respiratory Medicine Agonist medicine.medical_specialty Contraction (grammar) Physiology medicine.drug_class Bronchoconstriction Myocytes Smooth Muscle Inositol 1 4 5-Trisphosphate Permeability Potassium Chloride Bronchoconstrictor Agents Mice chemistry.chemical_compound Organ Culture Techniques Tetracaine Physiology (medical) Internal medicine medicine Animals Inositol 1 4 5-Trisphosphate Receptors Myocyte Inositol Calcium Signaling Anesthetics Local Lung Methacholine Chloride Calcium signaling Mice Inbred BALB C Ryanodine Chemistry Ryanodine receptor Temperature Ryanodine Receptor Calcium Release Channel Articles Cell Biology B vitamins Endocrinology Biophysics Calcium medicine.symptom Muscle Contraction Muscle contraction |
| Zdroj: | American Journal of Physiology-Lung Cellular and Molecular Physiology. 297:L347-L361 |
| ISSN: | 1522-1504 1040-0605 |
| DOI: | 10.1152/ajplung.90559.2008 |
| Popis: | The relative contribution of inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs) 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°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 IP3Rs and that tetracaine induces relaxation by both decreasing Ca2+ sensitivity and inhibiting agonist-induced Ca2+ oscillations via an IP3-dependent mechanism. |
| Databáze: | OpenAIRE |
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