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Reduced basal Ca2+ entry in pulmonary endothelial cells from chronically hypoxic rats is restored by administration of the scaffolding domain of caveolin‐1
Author(s) -
Gonzales Antonio J,
Riddle Melissa A.,
Paffett Michael L.,
Walker Benjimen R.
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.lb83
Subject(s) - transient receptor potential channel , hypoxia (environmental) , caveolin 1 , basal membrane , basal (medicine) , caveolae , endocrinology , medicine , chemistry , membrane potential , endothelium , receptor , biology , microbiology and biotechnology , signal transduction , biochemistry , pathology , oxygen , insulin , organic chemistry
Chronic hypoxia (CH)‐induced pulmonary hypertension is associated with impaired endothelial Ca 2+ influx in response to store depletion. Molecular candidates for store‐operated and receptor operated Ca 2+ entry (SOCE/ROCE) such as transient receptor potential (TRP) channels may also be involved in basal influx and appear to be trafficked to the plasma membrane by caveolin‐1 (cav‐1). We hypothesized that impaired basal Ca 2+ entry occurs following CH and is due to deficient cav‐1 mediated trafficking of relevant ion channels. Ca 2+ influx was assessed in isolated pressurized intrapulmonary arteries from control and CH rats (4 weeks at 0.5 atm) by Mn 2+ quenching of fura‐2 fluorescence in the presence of a cav‐1 scaffolding domain peptide (AP‐CAV) or scrambled control. AP‐CAV increased basal Ca 2+ influx in arteries from CH animals, and had no effect in the controls. In additional studies, we observed reduced immunofluorescent membrane localization of TRPC4 and cav‐1 in cultured bovine pulmonary artery endothelial cells (BPAECS) exposed to hypoxia (2% O 2 , 4 days) compared to controls. These studies suggest that hypoxia per se impairs cav‐1 mediated trafficking of ion channels that may be responsible for basal endothelial Ca 2+ influx.