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 language | English (US) |
|---|---|
| Pages (from-to) | 1594-1602 |
| Number of pages | 9 |
| Journal | Journal of Applied Physiology |
| Volume | 92 |
| Issue number | 4 |
| State | Published - 2002 |
| Externally published | Yes |
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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
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 journal › Article
}
TY - JOUR
T1 - Role of capacitative Ca2+ entry in bronchial contraction and remodeling
AU - Sweeney, Michele
AU - McDaniel, Sharon S.
AU - Platoshyn, Oleksandr
AU - Zhang, Shen
AU - Yu, Ying
AU - Lapp, Bethany R.
AU - Zhao, Ying
AU - Thistlethwaite, Patricia A.
AU - Yuan, Jason
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
KW - Asthma
KW - Store-operated cation channels
KW - Transient receptor potential gene
UR - http://www.scopus.com/inward/record.url?scp=0035999195&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035999195&partnerID=8YFLogxK
M3 - Article
C2 - 11896026
AN - SCOPUS:0035999195
VL - 92
SP - 1594
EP - 1602
JO - Journal of Applied Physiology
JF - Journal of Applied Physiology
SN - 8750-7587
IS - 4
ER -