Skip to main content

Research Repository

Advanced Search

Do sodium channel proteolytic fragments regulate sodium channel expression?

Onwuli, Donatus O.; Yañez-Bisbe, Laia; Pinsach-Abuin, Mel·lina; Tarradas, Anna; Brugada, Ramon; Greenman, John; Pagans, Sara; Beltran-Alvarez, Pedro


Donatus O. Onwuli

Laia Yañez-Bisbe

Mel·lina Pinsach-Abuin

Anna Tarradas

Ramon Brugada

Sara Pagans

Profile Image

Dr Pedro Beltran-Alvarez
Senior Lecturer in Health and Climate Change and Programme co-Director of the MSc Health and Climate Change


© 2017 Taylor & Francis The cardiac voltage-gated sodium channel (gene: SCN5A, protein: Na V 1.5) is responsible for the sodium current that initiates the cardiomyocyte action potential. Research into the mechanisms of SCN5A gene expression has gained momentum over the last few years. We have recently described the transcriptional regulation of SCN5A by GATA4 transcription factor. In this addendum to our study, we report our observations that 1) the linker between domains I and II (L DI-DII ) of Na V 1.5 contains a nuclear localization signal (residues 474–481) that is necessary to localize L DI-DII into the nucleus, and 2) nuclear L DI-DII activates the SCN5A promoter in gene reporter assays using cardiac-like H9c2 cells. Given that voltage-gated sodium channels are known targets of proteases such as calpain, we speculate that Na V 1.5 degradation is signaled to the cell transcriptional machinery via nuclear localization of L DI-DII and subsequent stimulation of the SCN5A promoter.


Onwuli, D. O., Yañez-Bisbe, L., Pinsach-Abuin, M., Tarradas, A., Brugada, R., Greenman, J., …Beltran-Alvarez, P. (2017). Do sodium channel proteolytic fragments regulate sodium channel expression?. Channels, 11(5), 476-481.

Journal Article Type Article
Acceptance Date May 26, 2017
Online Publication Date Aug 3, 2017
Publication Date Sep 3, 2017
Deposit Date Jul 9, 2018
Publicly Available Date Oct 27, 2022
Journal Channels
Print ISSN 1933-6950
Electronic ISSN 1933-6969
Publisher Taylor and Francis
Peer Reviewed Peer Reviewed
Volume 11
Issue 5
Pages 476-481
Keywords Voltage-gated sodium channel; Transcription factor; Gene expression; Nuclear localisation signal; Mutagenesis
Public URL
Publisher URL
Related Public URLs


You might also like

Downloadable Citations