A novel Ca2+ influx pathway activated by mechanical stretch in human airway smooth muscle cells

Satoru Ito, Hiroaki Kume, Keiji Naruse, Masashi Kondo, Naoya Takeda, Susumu Iwata, Yoshinori Hasegawa, Masahiro Sokabe

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

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) nonselective 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 [Ca 2+]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 Ca 2+ influx pathway activated by mechanical stretch, possibly through the Ca2+-permeable SA channel activated directly by stretch rather than by indirect mechanisms via intracellular messenger production, is involved in human airway smooth muscle cells. A molecular candidate for the putative SA channel may be one of the members of the TRPV channel family. Thus, abnormal Ca2+ homeostasis in response to excessive mechanical strain would contribute to the pathogenesis of asthma.

Original languageEnglish
Pages (from-to)407-413
Number of pages7
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume38
Issue number4
DOIs
Publication statusPublished - 01-04-2008
Externally publishedYes

Fingerprint

Smooth Muscle Myocytes
Muscle
1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole
Cells
Asthma
Transient Receptor Potential Channels
TRPV Cation Channels
Ruthenium Red
Cyclooxygenase Inhibitors
Type C Phospholipases
Silicones
Inositol
Nifedipine
Indomethacin
Smooth Muscle
Cations
Homeostasis
Membranes
xestospongin C
1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione

All Science Journal Classification (ASJC) codes

  • Cell Biology
  • Pulmonary and Respiratory Medicine
  • Molecular Biology

Cite this

Ito, Satoru ; Kume, Hiroaki ; Naruse, Keiji ; Kondo, Masashi ; Takeda, Naoya ; Iwata, Susumu ; Hasegawa, Yoshinori ; Sokabe, Masahiro. / A novel Ca2+ influx pathway activated by mechanical stretch in human airway smooth muscle cells. In: American Journal of Respiratory Cell and Molecular Biology. 2008 ; Vol. 38, No. 4. pp. 407-413.
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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; Kondo, Masashi; Takeda, Naoya; Iwata, Susumu; Hasegawa, Yoshinori; Sokabe, Masahiro.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 38, No. 4, 01.04.2008, p. 407-413.

Research output: Contribution to journalArticle

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AU - Ito, Satoru

AU - Kume, Hiroaki

AU - Naruse, Keiji

AU - Kondo, Masashi

AU - Takeda, Naoya

AU - Iwata, Susumu

AU - Hasegawa, Yoshinori

AU - Sokabe, Masahiro

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N2 - 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) nonselective 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 [Ca 2+]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 Ca 2+ influx pathway activated by mechanical stretch, possibly through the Ca2+-permeable SA channel activated directly by stretch rather than by indirect mechanisms via intracellular messenger production, is involved in human airway smooth muscle cells. A molecular candidate for the putative SA channel may be one of the members of the TRPV channel family. Thus, abnormal Ca2+ homeostasis in response to excessive mechanical strain would contribute to the pathogenesis of asthma.

AB - 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) nonselective 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 [Ca 2+]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 Ca 2+ influx pathway activated by mechanical stretch, possibly through the Ca2+-permeable SA channel activated directly by stretch rather than by indirect mechanisms via intracellular messenger production, is involved in human airway smooth muscle cells. A molecular candidate for the putative SA channel may be one of the members of the TRPV channel family. Thus, abnormal Ca2+ homeostasis in response to excessive mechanical strain would contribute to the pathogenesis of asthma.

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