Identification of N-terminal protein acetylation and arginine methylation of the voltage-gated sodium channel in end-stage heart failure human heart

J Mol Cell Cardiol. 2014 Nov;76:126-9. doi: 10.1016/j.yjmcc.2014.08.014. Epub 2014 Aug 27.


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.

Keywords: Arginine methylation; Heart failure; N-terminal acetylation; Post-translational modification; Proteomics; Voltage-gated sodium channel.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Amino Acid Sequence
  • Arginine / metabolism*
  • Cardiomyopathy, Dilated / metabolism
  • Heart Failure / metabolism*
  • Humans
  • Methylation
  • Myocardial Ischemia / metabolism
  • Myocardium / metabolism*
  • NAV1.5 Voltage-Gated Sodium Channel / metabolism*
  • Protein Processing, Post-Translational*


  • NAV1.5 Voltage-Gated Sodium Channel
  • SCN5A protein, human
  • Arginine