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Sulfenic Acid Modification of Kv1.5: A Redox‐Sensitive Fate Switch for Channel Surface Expression
Author(s) -
Svoboda Laurie Kathleen,
Reddie Khalilah G.,
Carroll Kate S.,
Martens Jeffrey R.
Publication year - 2010
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.24.1_supplement.770.2
Subject(s) - sulfenic acid , chemistry , oxidative stress , potassium channel , redox , oxidative phosphorylation , biophysics , microbiology and biotechnology , biochemistry , enzyme , biology , cysteine , organic chemistry
Atrial fibrillation, a life‐threatening arrhythmia, is strongly associated with oxidative stress. The voltage‐dependent potassium (Kv) channel, Kv1.5 is a prominent cardiovascular K + channel that is vital for atrial repolarization. Numerous studies suggest that Kv channels are redox‐sensitive; however, a molecular link between oxidative stress and altered Kv1.5 expression/activity has not been established. We have discovered that Kv1.5 is modified with sulfenic acid, a novel, redox‐sensitive posttranslational modification to this channel. In HL‐1 cells, stabilizing sulfenic acid during acute oxidative stress decreases Kv1.5 cell surface expression and channel current. Sulfenic acid modification inhibits recycling of internalized Kv1.5 back to the cell surface and promotes channel degradation after chronic oxidant exposure. Thus, sulfenic acid modification of Kv1.5 represents a fate switch, in which further oxidation diverts the channel from a recycling to a degradation pathway, providing a molecular link between oxidative stress and altered channel expression in atrial fibrillation. Support: NIHGrants HL0270973 and T32ES07062 and AHA Predoctoral Fellowship 0910001G.