Oxidative stress induces sulfenic acid modification of the Kv1.5 channel, reducing its cell surface density, which provides a molecular link to pro-arrhythmic changes in atrial fibrillation.
Oxidative modification may reduce Kv1.5 surface density; leaves open its contribution to atrial arrhythmogenesis.
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. Kv1.5 possesses intracellular cysteine residues that may be redox‐sensitive. Reversible formation of cysteine sulfenic acid in response to oxidative stress is a potentially important means of posttranslational protein regulation. Using a novel chemical probe, we find that Kv1.5 is modified with sulfenic acid in a redox‐sensitive manner. Mutagenesis to identify the redox‐sensitive cysteine residues reveals that sulfenic acid formation occurs on the COOH terminus. Using immunohistochemistry, we find that acute oxidant treatment decreases cell surface expression of Kv1.5, with no significant effect on Kv1.5 protein expression. Together, these data suggest that cellular redox state can induce formation of sulfenic acid and alter Kv1.5 cell surface density. Redox‐mediated alterations in cell surface density of ion channels may affect cellular excitability, leading to pro‐arrhythmic changes in cardiac action potentials. Research support: NIH Grants HL0270973 and T32ES07062.
No takes yet. Share an insight, caveat, or question.
Svoboda et al. (2009) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: