Role of capacitative Ca2+ entry in bronchial contraction and remodeling

Michele Sweeney, Sharon S. McDaniel, Oleksandr Platoshyn, Shen Zhang, Ying Yu, Bethany R. Lapp, Ying Zhao, Patricia A. Thistlethwaite, Jason X.J. Yuan

Research output: Contribution to journalArticlepeer-review

127 Scopus citations


Asthma is characterized by airway inflammation, bronchial hyperresponsiveness, and airway obstruction by bronchospasm and bronchial wall thickening due to smooth muscle hypertrophy. A rise in cytosolic free Ca2+ concentration ([Ca2+]cyt) may serve as a shared signal transduction element that causes bronchial constriction and bronchial wall thickening in asthma. In this study, we examined whether capacitative Ca2+ entry (CCE) induced by depletion of intracellular Ca2+ stores was involved in agonist-mediated bronchial constriction and bronchial smooth muscle cell (BSMC) proliferation. In isolated bronchial rings, acetylcholine (ACh) induced a transient contraction in the absence of extracellular Ca2+ because of Ca2+ release from intracellular Ca2+ stores. Restoration of extracellular Ca2+ in the presence of atropine, an M-receptor blocker, induced a further contraction that was apparently caused by a rise in [Ca2+]cyt due to CCE. In single BSMC, amplitudes of the store depletion-activated currents (ISOC) and CCE were both enhanced when the cells proliferate, whereas chelation of extracellular Ca2+ with EGTA significantly inhibited the cell growth in the presence of serum. Furthermore, the mRNA expression of TRPC1, a transient receptor potential channel gene, was much greater in proliferating BSMC than in growth-arrested cells. Blockade of the store-operated Ca2+ channels by Ni2+ decreased Isoc and CCE and markedly attenuated BSMC proliferation. These results suggest that upregulated TRPC1 expression, increased Isoc, enhanced CCE, and elevated [Ca2+]cyt may play important roles in mediating bronchial constriction and BSMC proliferation.

Original languageEnglish (US)
Pages (from-to)1594-1602
Number of pages9
JournalJournal of Applied Physiology
Issue number4
StatePublished - 2002
Externally publishedYes


  • Asthma
  • Store-operated cation channels
  • Transient receptor potential gene

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


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