<figure><img src="image_1.png" /></figure>

HAL
open science

# Dynamics of cardiac Nav1.5 channel complexes upon an acute $\beta$-adrenergic stimulation

Floriane Bibault, Kristell Mimoun, Daniel Maloney, Reid R Townsend, Jeanne

M Nerbonne, Jonathan R Silva, Céline Marionneau

► To cite this version:

Floriane Bibault, Kristell Mimoun, Daniel Maloney, Reid R Townsend, Jeanne M Nerbonne, et al. Dynamics of cardiac Nav1.5 channel complexes upon an acute $\beta$-adrenergic stimulation. Worldwide Sodium Channel Conference 2024, Hugues Abriel, Jan 2024, Grindelwald, Suisse, Switzerland. hal-04753905

HAL Id: hal-04753905

https://hal.science/hal-04753905v1

Submitted on 25 Oct 2024

HAL is a multi-disciplinary open access
archive for the deposit and dissemination of sci-
entific research documents, whether they are pub-
lished or not. The documents may come from
teaching and research institutions in France or
abroad, or from public or private research centers.

L'archive ouverte pluridisciplinaire HAL, est
destinée au dépôt et à la diffusion de documents
scientifiques de niveau recherche, publiés ou non,
émanant des établissements d'enseignement et de
recherche français ou étrangers, des laboratoires
publics ou privés.

Public Domain
Dynamics of cardiac Nav1.5 channel complexes upon an acute β-adrenergic stimulation

Floriane Bibault, Kristell Mimoun, Daniel Maloney, Reid R Townsend, Jeanne M Nerbonne, Jonathan R Silva and Céline Marionneau

Nantes Université, CNRS, INSERM, l'institut du thorax, F-44000 Nantes, France
Bioinformatics Solutions Inc., Waterloo, ON, Canada

Department of Biomedical Engineering, Washington University in Saint Louis, Saint Louis, MO, USA

Departments of Cell Biology and Physiology, Medicine and Developmental Biology, Washington University Medical School, Saint Louis, MO, USA

Voltage-gated sodium (Nav) channels, generated by the pore-forming α subunit Nav1.5, are responsible for the initiation and fast propagation of action potentials in atrial and ventricular myocytes, and dysregulation of these channels underlies diverse types of inherited and acquired cardiac arrhythmias. Native cardiac Nav1.5-encoded channels function in macromolecular protein complexes, containing a variety of intracellular and transmembrane accessory proteins that influence channel expression, functioning and post-translational modifications (PTMs). To identify the dynamics of PTMs of Nav1.5 and associated accessory proteins in native cardiac Nav1.5-encoded channels, we have developed unbiased mass spectrometry-based phosphoproteomic approaches. Here, we report the results of recent studies focused on the dynamics of ventricular Nav1.5-encoded channels in the context of acute β-adrenergic receptor stimulation. Our findings revealed that the Nav1.5 protein undergoes a dramatic increase in phosphorylation at five distinct, non-adjacent sites, four of which have not been previously identified. Interestingly, while the abundance of previously suggested accessory/regulatory proteins of Nav1.5 was not changed, β-adrenergic receptor stimulation decreased the abundance of what appears to be a novel Nav1.5 channel accessory protein, Bcl2-associated athanogene 2, Bag2. Together, these novel findings challenge the conventional view that native ion channels are regulated by phosphorylation at one or two nearby phosphosites on the pore-forming subunit and/or on associated accessory proteins, and suggest that phosphorylation leads to secondary structures that become acceptors of new protein interactions.