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1 Department of Anesthesiology, Mayo Clinic College of Medicine, 4-184 W Jos SMH, Rochester, Minnesota, 55905, United States; Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, Minnesota, United States
2 Department of Anesthesiology, Mayo Clinic College of Medicine, Rochester, Minnesota, United States
3 Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, Minnesota, United States
4 Department of Anesthesiology, Mayo Clinic College of Medicine, 4-184 W Jos SMH, Rochester, Minnesota, 55905, United States
5 Department of Anesthesiology, Mayo Clinic College of Medicine, Rochester, Minnesota, United States; Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, 55905, Minnesota, United States
* To whom correspondence should be addressed. E-mail: prakash.ys{at}mayo.edu.
Regulation of intracellular Ca2+ [Ca2+]i is key to airway smooth muscle (ASM) tone. In vascular smooth muscle, specialized membrane microdomains (caveolae) expressing the scaffolding protein caveolin-1 are thought to facilitate cellular signal transduction. In human ASM cells, we tested the hypothesis that caveolae mediate Ca2+ responses to agonist stimulation. Fluorescence immunocytochemistry with confocal microscopy as well as Western blot analysis were used to determine that agonist receptors (M3 muscarinic, bradykinin, histamine) and store-operated Ca2+ entry (SOCE) regulatory mechanisms co-localize with caveolin-1. While caveolin-2 co-expressed with caveolin-1, caveolin-3 was absent. In fura-2 loaded ASM cells, [Ca2+]i responses to 1µM ACh, 10µM histamine and 10nM bradykinin, as well as SOCE were all attenuated (albeit to different extents) following disruption of caveolae by the cholesterol chelating drug, methyl-
-cyclodextrin. Transfection of ASM cells with 50nM caveolin-1 siRNA significantly knocked down caveolin-1 expression, and blunted [Ca2+]i responses to bradykinin and histamine (but less so for ACh), as well as SOCE. These results indicate that caveolae are present in ASM, and caveolin-1 contributes to regulation of [Ca2+]i responses to agonist.
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