Abstract
The α subunit of the cardiac voltage-gated sodium channel, Naᵥ1.5, provides the rapid sodium inward current that initiates cardiomyocyte action potentials. Here, we analyzed for the first time the post-translational modifications of Naᵥ1.5 purified from end-stage heart failure human cardiac tissue. We identified R526 methylation as the major post-translational modification of any Naᵥ1.5 arginine or lysine residue. Unexpectedly, we found that the N terminus of Naᵥ1.5 was: 1) devoid of the initiation methionine, and 2) acetylated at the resulting initial alanine residue. This is the first evidence for N-terminal acetylation in any member of the voltage-gated ion channel superfamily. Our results open the door to explore Naᵥ1.5 N-terminal acetylation and arginine methylation levels as drivers or markers of end-stage heart failure.
Citation
Beltran-Alvarez, P., Tarradas, A., Chiva, C., Pérez-Serra, A., Batlle, M., Pérez-Villa, F., Schulte, U., Sabidó, E., Brugada, R., & Pagans, S. (2014). Identification of N-terminal protein acetylation and arginine methylation of the voltage-gated sodium channel in end-stage heart failure human heart. Journal of Molecular and Cellular Cardiology, 76, 126-129. https://doi.org/10.1016/j.yjmcc.2014.08.014