Premium
Arachidonate‐regulated channels (ARC) and intracellular Ca 2+ regulation in human airway smooth muscle
Author(s) -
Thompson Michael A,
Pabelick Christina M,
Prakash Y S
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.1062.7
Subject(s) - ryanodine receptor , arachidonic acid , chemistry , endoplasmic reticulum , serca , biophysics , intracellular , thapsigargin , endocrinology , medicine , microbiology and biotechnology , biochemistry , biology , atpase , enzyme
Plasma membrane Ca 2+ influx and sarcoplasmic reticulum (SR) Ca 2+ release are key components of intracellular Ca 2+ regulation in airway smooth muscle (ASM). We and others have previously found that ASM Ca 2+ regulation involves propagating Ca 2+ oscillations via these mechanisms. Ca 2+ oscillations in non‐excitable cells involve influx via arachidonic acid (AA) regulated channels (ARC); however, little is known about ARC in ASM. In human ASM cells loaded with fura2 (5 μM), we found that 10 μM AA triggered Ca 2+ oscillations. OAG, oleic acid and palmitic acid (10 μM) failed to elicit Ca 2+ responses. Pre‐incubation with LaCl 3 1 μM and 1mM; 5 min) inhibited AA‐induced oscillations. Inhibition of SR Ca 2+ release (ryanodine 10 μM and IP3 channel inhibitor Xestospongin C 10 μM; 30 min), decreased Ca 2+ oscillation frequency and amplitude. Inhibitors of receptor‐operated channels (SKF‐96365; 10 μM), lipoxygenase (zileuton; 10 μM), or cyclooxygenase (indomethacin; 1 μM), did not affect oscillations. Finally, siRNA for Caveolin‐1, STIM1 and Orai3 (25nM) reduced frequency and amplitude of AA‐induced oscillations. These results indicate a novel caveolar Ca 2+ influx mechanism in human ASM mediated via AA that interacts with SR to produce repetitive SR Ca 2+ release. Such AA‐mediated influx could potentially contribute to increased Ca 2+ in ASM during inflammation. Supported by NIH grants HL090595 (CMP) and HL088029 (YSP)