Premium
Ceramide induces inhibition of Kv channels and vasoconstriction in rat pulmonary arteries
Author(s) -
Frazziano Giovanna,
Cobeño Laura,
Cogolludo Angel,
Moreno Laura,
Moral Javier,
Villamor Eduardo,
PerezVizcaino Francisco
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.22.1_supplement.1174.8
Subject(s) - hypoxic pulmonary vasoconstriction , nadph oxidase , protein kinase c , ceramide , mesenteric arteries , apocynin , vasoconstriction , medicine , sphingomyelin phosphodiesterase , endocrinology , reactive oxygen species , vascular smooth muscle , biology , chemistry , microbiology and biotechnology , phosphorylation , biochemistry , artery , apoptosis , smooth muscle
Voltage‐gated potassium (Kv) channels make a major contribution to the membrane potential of pulmonary artery smooth muscle cells (PASMC). We examined whether ceramide, a sphingolipid‐derived second messenger, inhibits Kv channels and induces pulmonary vasoconstriction. C6‐ceramide and bacterial sphingomyelinase inhibited Kv currents and caused depolarization of freshly isolated PASMC and induced a sustained contractile response in endothelium–denuded pulmonary arteries. C6‐ceramide also increased the production of reactive oxygen species, measured by the fluorescence of dichlorofluorescein. The protein kinase Cζ (PKCζ) pseudosubstrate inhibitor (PKC‐PI) inhibited all the effects elicited by C6‐ceramide. t‐butyl‐hydroperoxide inhibited Kv currents and contracted pulmonary arteries but these effects were not affected by PKCζ‐PI. The NADPH oxidase inhibitor apocynin prevented the C6‐ceramide‐induced Kv current inhibition and vasoconstriction. In contrast to pulmonary arteries, in mesenteric arteries, C6‐ceramide had no effect on either Kv currents or resting tone. The expression of Kv1.5 and PKCζ was significantly higher in pulmonary compared to mesenteric arteries. In conclusion, ceramide induced a pulmonary‐selective inhibition of Kv currents and vasoconstriction via PKCζ and NADPH‐oxidase derived reactive oxygen species