Abstract
Voltage-gated sodium channels are essential proteins in brain physiology, as they generate the sodium currents that initiate neuronal action potentials. Voltage-gated sodium channels expression, localisation and function are regulated by a range of transcriptional and post-translational mechanisms. Here, we review our understanding of regulation of brain voltage-gated sodium channels, in particular SCN1A (NaV1.1), SCN2A (NaV1.2), SCN3A (NaV1.3) and SCN8A (NaV1.6), by transcription factors, by alternative splicing, and by post-translational modifications. Our focus is strongly centred on recent research lines, and newly generated knowledge.
Highlights
Voltage-gated sodium channels are essential proteins in brain physiology
We have considered the main sodium channel isoforms expressed in the central neuronal system (CNS), i.e., SCN1A (NaV1.1), SCN2A (NaV1.2), SCN3A (NaV1.3) and SCN8A (NaV1.6)
Regulation of brain sodium channel expression at the transcriptional level we have considered the regulation of CNS voltage-gated sodium channels by transcription factors, and by alternative splicing
Summary
Voltage-gated sodium channels are essential proteins in brain physiology. Upon voltage-mediated activation, sodium channels produce sodium currents responsible for depolarisation of excitable cells, including neurons and cardiomyocytes. BACE1-dependent sodium channel expression seems to be specific for NaV1.1, and mRNA levels of other brain NaV isoforms including NaV1.2, NaV1.3 and NaV1.6 are relatively insensitive to BACE1 protease activity (Kim et al 2007, 2011). Arginine methylation has recently been reported as a novel post-translational modification of the voltage-gated sodium channel family using NaV1.5 as a model system (Beltran-Alvarez et al 2011). NaV1.5 peptide containing R513 is methylated in vitro by PRMT3 (Beltran-Alvarez et al 2015) Another well-known PTM, N-glycosylation, has been mostly studied in the cardiac isoform of the sodium channel, and several excellent reviews have recently been published (Baycin-Hizal et al 2014; Marionneau and Abriel 2015). Perhaps the latest studies are those from the Chatelier and the Decosterd–Abriel groups, which have proposed alternative trafficking pathways for differentially glycosylated NaV, using NaV1.5 and NaV1.7 as study models (Mercier et al 2015; Laedermann et al 2013, respectively)
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