A Distinct Pool of Nav1.5 Channels at the Lateral Membrane of Murine Ventricular Cardiomyocytes.
Détails
Télécharger: fphys-10-00834.pdf (5147.60 [Ko])
Etat: Public
Version: Final published version
Licence: CC BY 4.0
Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_2CDD56FC25F9
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
A Distinct Pool of Nav1.5 Channels at the Lateral Membrane of Murine Ventricular Cardiomyocytes.
Périodique
Frontiers in physiology
ISSN
1664-042X (Print)
ISSN-L
1664-042X
Statut éditorial
Publié
Date de publication
2019
Peer-reviewed
Oui
Volume
10
Pages
834
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Publication Status: epublish
Résumé
Background: In cardiac ventricular muscle cells, the presence of voltage-gated sodium channels Na <sub>v</sub> 1.5 at the lateral membrane depends in part on the interaction between the dystrophin-syntrophin complex and the Na <sub>v</sub> 1.5 C-terminal PDZ-domain-binding sequence Ser-Ile-Val (SIV motif). α1-Syntrophin, a PDZ-domain adaptor protein, mediates the interaction between Na <sub>v</sub> 1.5 and dystrophin at the lateral membrane of cardiac cells. Using the cell-attached patch-clamp approach on cardiomyocytes expressing Na <sub>v</sub> 1.5 in which the SIV motif is deleted (ΔSIV), sodium current (I <sub>Na</sub> ) recordings from the lateral membrane revealed a SIV-motif-independent I <sub>Na</sub> . Since immunostaining has suggested that Na <sub>v</sub> 1.5 is expressed in transverse (T-) tubules, this remaining I <sub>Na</sub> might be carried by channels in the T-tubules. Of note, a recent study using heterologous expression systems showed that α1-syntrophin also interacts with the Na <sub>v</sub> 1.5 N-terminus, which may explain the SIV-motif independent I <sub>Na</sub> at the lateral membrane of cardiomyocytes. Aim: To address the role of α1-syntrophin in regulating the I <sub>Na</sub> at the lateral membrane of cardiac cells. Methods and Results: Patch-clamp experiments in cell-attached configuration were performed on the lateral membranes of wild-type, α1-syntrophin knockdown, and ΔSIV ventricular mouse cardiomyocytes. Compared to wild-type, a reduction of the lateral I <sub>Na</sub> was observed in myocytes from α1-syntrophin knockdown hearts. Similar to ΔSIV myocytes, a remaining I <sub>Na</sub> was still recorded. In addition, cell-attached I <sub>Na</sub> recordings from lateral membrane did not differ significantly between non-detubulated and detubulated ΔSIV cardiomyocytes. Lastly, we obtained evidence suggesting that cell-attached patch-clamp experiments on the lateral membrane cannot record currents carried by channels in T-tubules such as calcium channels. Conclusion: Altogether, these results suggest the presence of a sub-pool of sodium channels at the lateral membrane of cardiomyocytes that is independent of α1-syntrophin and the PDZ-binding motif of Na <sub>v</sub> 1.5, located in membrane domains outside of T-tubules. The question of a T-tubular pool of Na <sub>v</sub> 1.5 channels, however, remains open.
Mots-clé
dystrophin, electrophysiology, lateral membrane of cardiomyocytes, voltage-gated sodium channel, α1-syntrophin
Pubmed
Web of science
Open Access
Oui
Création de la notice
02/08/2019 17:12
Dernière modification de la notice
13/12/2019 8:08