| Autor: |
Sweeney, Michele, McDaniel, Sharon S., Platoshyn, Oleksandr, Zhang, Shen, Yu, Ying, Lapp, Bethany R., Zhao, Ying, Thistlethwaite, Patricia A., Yuan, Jason X.-J. |
| Zdroj: |
Journal of Applied Physiology; April 2002, Vol. 92 Issue: 4 p1594-1602, 9p |
| Abstrakt: |
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+]cytdue 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 ISOCand CCE and markedly attenuated BSMC proliferation. These results suggest that upregulated TRPC1 expression, increasedISOC, enhanced CCE, and elevated [Ca2+]cytmay play important roles in mediating bronchial constriction and BSMC proliferation. |
| Databáze: |
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