Premium
Cytoplasmic and mitochondrial‐produced superoxide mediates angiotensin II (AngII)‐induced inhibition of K+ current in CATH.a neurons
Author(s) -
Yin JingXiang,
Li YuLong,
Xiao Liang,
Schultz Harold D.,
Zimmerman Matthew C.
Publication year - 2008
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.22.2_supplement.150
Subject(s) - angiotensin ii , superoxide dismutase , intracellular , extracellular , chemistry , reactive oxygen species , superoxide , cytoplasm , patch clamp , mitochondrion , pharmacology , medicine , endocrinology , microbiology and biotechnology , biology , oxidative stress , biochemistry , receptor , enzyme
Reactive oxygen species, such as superoxide (O 2 •− ) and hydrogen peroxide, have been identified as key signaling intermediates in AngII‐induced neuronal activation and sympathoexcitation associated with heart failure and hypertension. Here, we hypothesized that AngII‐induced inhibition of the delayed rectifier K + current (I Kv ) is mediated specifically by intracellular O 2 •− . Differentiated CATH.a neurons were infected with adenoviral vectors (50 MOI) encoding the primarily cytoplasmic‐localized O 2 •− dismutase (CuZnSOD), or the mitochondrial‐targeted isoform (MnSOD). Four days later, I Kv was recorded using the whole cell configuration of the patch‐clamp technique. In non‐infected and control vector (AdEmpty)‐infected neurons, AngII (100 nM) decreased the density of I Kv by 45 ± 4% and 37 ± 6%, respectively (I Kv elicited by 400 ms pulse from −80 to +80 mV, P<0.05 vs vehicle). This AngII effect was significantly blunted in neurons overexpressing active MnSOD or CuZnSOD as AngII inhibited I Kv by merely 18 ± 8% and 11 ± 3%, respectively (P<0.05 vs AdEmpty‐treated and non‐infected cells). In contrast, extracellular SOD protein (400 U/ml)‐treated cells exhibited the characteristic AngII‐induced inhibition of I Kv (34 ± 7%). These data suggest that intracellular O 2 •− produced from both cytoplasmic and mitochondrial sources attenuates AngII‐induced inhibition of I Kv in neurons. NIH P20RR017675; P01HL062222