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Redox control of oxygen sensing in the rabbit ductus arteriosus
Author(s) -
Reeve Helen L.,
Tolarova Simona,
Nelson Daniel P.,
Archer Stephen,
Weir E. Kenneth
Publication year - 2001
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.2001.0253b.x
Subject(s) - chemistry , catalase , dithiothreitol , intracellular , membrane potential , superoxide dismutase , depolarization , reactive oxygen species , extracellular , ductus arteriosus , biophysics , endogeny , medicine , endocrinology , oxidative stress , biochemistry , biology , enzyme
How the ductus arteriosus (DA) closes at birth remains unclear. Inhibition of O 2 ‐sensitive K + channels may initiate the closure but the sensor mechanism is unknown. We hypothesized that changes in endogenous H 2 O 2 could act as this sensor. Using chemiluminescence measurements with luminol (50 μ m ) or lucigenin (5 μ m ) we showed significantly higher levels of reactive O 2 species in normoxic, compared to hypoxic DA. This increase in chemiluminescence was completely reversed by catalase (1200 U ml −1 ). Prolonged normoxia caused a significant decrease in K + current density and depolarization of membrane potential in single fetal DA smooth muscle cells. Removal of endogenous H 2 O 2 with intracellular catalase (200 U ml −1 ) increased normoxic whole‐cell K + currents ( I K ) and hyperpolarized membrane potential while intracellular H 2 O 2 (100 n m ) and extracellular t‐butyl H 2 O 2 (100 μ m ) decreased I K and depolarized membrane potential. More rapid metabolism of O 2 − · with superoxide dismutase (100 U ml −1 ) had no significant effect on normoxic K + currents.N ‐Mercaptopropionylglycine (NMPG), duroquinone and dithiothreitol all dilated normoxic‐constricted DA rings, while the oxidizing agent 5,5′‐dithiobis‐(2‐nitrobenzoic acid) constricted hypoxia‐dilated rings. NMPG also increased I K . We conclude that increased H 2 O 2 levels, associated with a cytosolic redox shift at birth, signal K + channel inhibition and DA constriction.