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The role of calcium‐activated chloride channels to serotonin‐mediated pulmonary arterial tone is influenced by postnatal maturation
Author(s) -
Vemulakonda Srilakshmi,
Angermann Jeff,
Vranken Kurt,
Papamatheakis Demosthenes,
Nguyen Dan,
Dawson Antoinette,
Blood Arlin B,
Pearce William J,
Longo Lawrence,
Wilson Sean M
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.999.1
Subject(s) - niflumic acid , chloride channel , depolarization , electrical impedance myography , medicine , fetus , serotonin , endocrinology , vasoconstriction , pulmonary hypertension , calcium , chemistry , anatomy , cardiology , biology , vasodilation , biochemistry , receptor , pregnancy , genetics
Agonists can induce pulmonary arterial contractility through membrane depolarization and resultant cytosolic Ca 2+ increases. The specific mechanism(s) involved in the depolarization process remain controversial, but evidence indicates calcium‐activated chloride channels (ClCa) are pivotal. Our previous investigations show the role of L‐type Ca 2+ channels is depressed in fetus relative to adult, and thus we were interested in testing the hypothesis that the role for ClCa changes in parallel. This hypothesis was assessed by wire‐myography of isolated pulmonary arteries from fetus and adult, and confocal imaging of Ca 2+ in fluo‐4 loaded arteries. Pulmonary arterial constriction to 10 μM serotonin (5‐HT) in adult was substantially inhibited by the ClCa blocker niflumic acid (NFA; 100 μM). In comparison, NFA did not reduce tension in 5‐HT contracted pulmonary arteries from fetus or 15 day‐old lambs. Confocal microscopy of fetal pulmonary arteries showed NFA also failed to reduce Ca 2+ ‐dependent signaling, which we presume to be the mechanism underlying the ability of NFA to reduce arterial tension. These studies provide the first report indicating developmental progression in ClCa functionality in the pulmonary vasculature. Support from NSF, NIH, UM, and LLUMC.