La. Shimoda et al., L-type Ca2+ channels, resting [Ca2+](i), and ET-1-induced responses in chronically hypoxic pulmonary myocytes, AM J P-LUNG, 279(5), 2000, pp. L884-L894
Citations number
50
Categorie Soggetti
da verificare
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
In the lung, chronic hypoxia (CH) causes pulmonary arterial smooth muscle c
ell (PASMC) depolarization, elevated endothelin-1 (ET-1), and vasoconstrict
ion. We determined whether, during CH, depolarization-driven activation of
L-type Ca2+ channels contributes to 1) maintenance of resting intracellular
Ca2+ concentration ([Ca2+](i)), 2) increased [Ca2+](i) in response to ET-1
(10(-8) M), and 3) ET-1-induced contraction. Using indo 1 microfluorescenc
e, we determined that resting [Ca2+](i) in PASMCs from intrapulmonary arter
ies of rats exposed to 10% O-2 for 21 days was 293.9 +/- 25.2 nM (vs. 153.6
+/- 28.7 nM in normoxia). Resting [Ca 21]i was decreased after extracellul
ar Ca2+ removal but not with nifedipine (10(-6) M), an L-type Ca2+ channel
antagonist. After CH, the ET-1-induced increase in [Ca2+](i) was reduced an
d was abolished after extracellular Ca2+ removal or nifedipine. Removal of
extracellular Ca2+ reduced ET-1-induced tension; however, nifedipine had on
ly a slight effect. These data indicate that maintenance of resting [Ca2+](
i) in PASMCs from chronically hypoxic rats does not require activation of L
-type Ca2+ channels and suggest that ET-1-induced contraction occurs by a m
echanism primarily independent of changes in [Ca2+](i).