Abstract

The alpha-subunit of the cardiac voltage-gated sodium channel (Na(V)1.5) plays a central role in cardiomyocyte excitability. We have recently reported that Na(V)1.5 is post-translationally modified by arginine methylation. Here, we aimed to identify the enzymes that methylate Na(V)1.5, and to describe the role of arginine methylation on Na(V)1.5 function. Our results show that protein arginine methyl transferase (PRMT)-3 and -5 methylate Na(V)1.5 in vitro, interact with Na(V)1.5 in human embryonic kidney (HEK) cells, and increase Na(V)1.5 current density by enhancing Na(V)1.5 cell surface expression. Our observations are the first evidence of regulation of a voltage-gated ion channel, including calcium, potassium, sodium and TRP channels, by arginine methylation. Structured digital abstract: PRMT5 physically interacts with Nav1.5 by fluorescent resonance energy transfer (View interaction) PRMT3 physically interacts with Nav1.5 by fluorescent resonance energy transfer (View interaction) Nav1.5 physically interacts with PRMT3 by anti tag coimmunoprecipitation (View interaction) PRMT1 physically interacts with Nav1.5 by fluorescent resonance energy transfer (View interaction) Nav1.5 physically interacts with PRMT1 by anti tag coimmunoprecipitation (View interaction) (C) 2013 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.