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 Yuan

Research output: Contribution to journalArticle

122 Citations (Scopus)

Abstract

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
Volume92
Issue number4
StatePublished - 2002
Externally publishedYes

Fingerprint

Smooth Muscle Myocytes
Bronchoconstriction
Cell Proliferation
Asthma
Transient Receptor Potential Channels
Bronchial Spasm
Egtazic Acid
Airway Obstruction
Growth
Atropine
Hypertrophy
Acetylcholine
Smooth Muscle
Signal Transduction
Inflammation
Messenger RNA
Serum
Genes

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Orthopedics and Sports Medicine
  • Physical Therapy, Sports Therapy and Rehabilitation

Cite this

Sweeney, M., McDaniel, S. S., Platoshyn, O., Zhang, S., Yu, Y., Lapp, B. R., ... Yuan, J. (2002). Role of capacitative Ca2+ entry in bronchial contraction and remodeling. Journal of Applied Physiology, 92(4), 1594-1602.

Role of capacitative Ca2+ entry in bronchial contraction and remodeling. / Sweeney, Michele; McDaniel, Sharon S.; Platoshyn, Oleksandr; Zhang, Shen; Yu, Ying; Lapp, Bethany R.; Zhao, Ying; Thistlethwaite, Patricia A.; Yuan, Jason.

In: Journal of Applied Physiology, Vol. 92, No. 4, 2002, p. 1594-1602.

Research output: Contribution to journalArticle

Sweeney, M, McDaniel, SS, Platoshyn, O, Zhang, S, Yu, Y, Lapp, BR, Zhao, Y, Thistlethwaite, PA & Yuan, J 2002, 'Role of capacitative Ca2+ entry in bronchial contraction and remodeling', Journal of Applied Physiology, vol. 92, no. 4, pp. 1594-1602.
Sweeney M, McDaniel SS, Platoshyn O, Zhang S, Yu Y, Lapp BR et al. Role of capacitative Ca2+ entry in bronchial contraction and remodeling. Journal of Applied Physiology. 2002;92(4):1594-1602.
Sweeney, Michele ; McDaniel, Sharon S. ; Platoshyn, Oleksandr ; Zhang, Shen ; Yu, Ying ; Lapp, Bethany R. ; Zhao, Ying ; Thistlethwaite, Patricia A. ; Yuan, Jason. / Role of capacitative Ca2+ entry in bronchial contraction and remodeling. In: Journal of Applied Physiology. 2002 ; Vol. 92, No. 4. pp. 1594-1602.
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