La. Shimoda et al., Mobilization of intracellular Ca2+ by endothelin-1 in rat intrapulmonary arterial smooth muscle cells, AM J P-LUNG, 278(1), 2000, pp. L157-L164
Citations number
45
Categorie Soggetti
da verificare
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
Endothelin-1 (ET-1) increases intracellular Ca2+ concentration ([Ca2+](i))
in pulmonary arterial smooth muscle cells (PASMCs); however, the mechanisms
for Ca2+ mobilization are not clear. We determined the contributions of ex
tracellular influx and intracellular release to the ET-1-induced Ca2+ respo
nse using Indo 1 fluorescence and electrophysiological techniques. Applicat
ion of ET-1 (10(-10) to 10(-8) M) to transiently (24-48 h) cultured rat PAS
MCs caused concentration-dependent increases in [Ca2+](i). At 10(-8) M, ET-
1 caused a large, transient increase in [Ca2+](i) (>1 mu M) followed by a s
ustained elevation in [Ca2+](i) (<200 nM). The ET-1-induced increase in [Ca
2+](i) was attenuated (<80%) by extracellular Ca2+ removal; by verapamil, a
voltage-gated Ca2+-channel antagonist; and by ryanodine, an inhibitor of C
a2+ release from caffeine-sensitive stores. Depleting intracellular stores
with thapsigargin abolished the peak in [Ca2+](i), but the sustained phase
was unaffected. Simultaneously measuring membrane potential and [Ca2+](i) i
ndicated that depolarization preceded the rise in [Ca2+](i). These results
suggest that ET-1 initiates depolarization in PASMCs, leading to Ca2+ influ
x through voltage-gated Ca2+ channels and Ca2+ release from ryanodine- and
inositol 1,4,5-trisphosphate-sensitive stores.