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Membrane cholesterol facilitates agonist‐induced calcium entry in pulmonary arterial endothelium
Author(s) -
Zhang Bojun,
Naik Jay,
Resta Thomas,
Walker Benjimen
Publication year - 2013
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.27.1_supplement.724.7
Subject(s) - agonist , calcium , cholesterol , chemistry , endocrinology , medicine , biochemistry , biology , receptor
ATP‐induced calcium entry(ATP‐CE) along with membrane cholesterol levels are reduced in pulmonary artery endothelial cells (PAECs) from rats exposed to chronic hypoxia (CH; 4 wk, P B = 380 torr). Furthermore, supplementation of membrane cholesterol restores ATP‐CE in PAECs from CH rats without affecting controls. To further elucidate the role of membrane cholesterol in agonist‐induced calcium entry, we studied on PAECs from control animals. We hypothesized that PAEC membrane cholesterol facilitates agonist‐induced calcium entry. To test this hypothesis, we administered the cholesterol depleting agent methyl‐β cyclodextrin (MβCD) or vehicle to isolated PAEC sheets from control rats and assessed ATP‐CE with fura‐2 fluorescence. Calcium entry was reduced in PAECs treated with MβCD compared to controls. Treatment with epicholesterol (epimeric form of cholesterol) similarly decreased ATP‐CE. In contrast, cholesterol‐saturated MβCD had no effect on ATP‐CE. We conclude that membrane cholesterol facilitates agonist‐induced calcium entry in PAECs and that t he reduced influx seen after CH is possibly due to loss of this key regulator. Supported by NIH grant HL95640.