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Caveolin‐1 scaffolding domain restores endothelial membrane potential and vasoconstrictor reactivity following chronic hypoxia
Author(s) -
Riddle Melissa A,
Walker Benjimen R
Publication year - 2011
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.25.1_supplement.1042.11
Subject(s) - chemistry , phenylephrine , hyperpolarization (physics) , vasoconstriction , vasodilation , endocrinology , medicine , membrane potential , hypoxia (environmental) , endothelial stem cell , electrical impedance myography , caveolae , endothelium , biophysics , signal transduction , biochemistry , biology , oxygen , stereochemistry , in vitro , organic chemistry , nuclear magnetic resonance spectroscopy , blood pressure
Chronic hypoxia (CH) causes diminished vasoconstrictor reactivity due to activation of endothelial cell (EC) large conductance Ca 2+ ‐activated K + channels (BK Ca ) channels. In addition, EC BK Ca channel activity appears to be inhibited by the scaffolding domain of caveolin‐1 (Cav‐1). We hypothesized that CH exposure results in a loss of Cav‐1 inhibition of EC BK Ca channels leading to EC hyperpolarization and diminished vasoconstrictor reactivity. To test this hypothesis, we administered a cell permeant scaffolding domain peptide of Cav‐1 (AP‐CAV) or scrambled control peptide to gracilis arterioles from control and CH (P B = 380 torr for 48 hr) rats to restore possible Cav‐1 inhibition EC BK Ca . EC membrane potential measured with sharp electrodes was hyperpolarized in arteries from CH rats compared to controls, but was normalized by AP‐CAV. AP‐CAV had no effect on membrane potential in arterioles from control rats. Further, videomicroscopy showed that luminal AP‐CAV restored both myogenic tone and vasoconstrictor reactivity to phenylephrine in vessels from CH rats to levels of controls. Again, AP‐CAV did not alter reactivity of control arteries. Scrambled peptide was without effect in all studies. We conclude that deranged Cav‐1 function following CH results in activation of endothelial BK Ca channels leading to EC hyperpolarization and diminished vasoconstriction.