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A Novel Ca2+ Influx Pathway Activated by Mechanical Stretch in Human Airway Smooth Muscle Cells
ITO Satoru ; KUME Hiroaki ; NARUSE Keiji ; ...
In response to mechanical stretch, airway smooth muscle exhibits various cellular functions such as contraction, proliferation, and cytoskeletal remodeling, all of which are implicated in the pathophysiology of asthma. We tested the hypothesis that mechanical stretch of airway smooth muscle cells increases intracellular Ca2+ concentration ([Ca2+]i) by activating stretch-activated (SA) non-selective cation channels. A single uniaxial stretch (3 s) was given to human bronchial smooth muscle cells cultured on an elastic silicone membrane. After the mechanical stretch, a transient increase in [Ca2+]i was observed. The [Ca2+]i increase was significantly dependent on stretch amplitude. The augmented [Ca2+]i due to stretch was completely abolished by removal of extracellular Ca2+ and was markedly attenuated by an application of Gd3+, an inhibitor of SA channels, or ruthenium red, a transient receptor potential vanilloid (TRPV) inhibitor. In contrast, the stretch-induced rises of [Ca2+]i were not altered by other Ca2+ channel inhibitors such as nifedipine, BTP-2, and SKF-96365. Moreover, the [Ca2+]i increases were not affected by indomethacin, a cyclooxygenase inhibitor, U-73122, a phospholipase C inhibitor, or xestospongin C, an inhibitor of the inositol-trisphosphate receptor. These findings demonstrate that a novel Ca2+ influx pathway activated by mechanical stretch, possibly thro
American Lung Association
PMID : 17975175 ISSN : 1044-1549 CODEN : AJRBEL
American journal of respiratory cell and molecular biology A. 2008, vol. 38, n° 4, pp. 407-413 [7 pages]
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