A Distinct Pool of Nav1.5 Channels at the Lateral Membrane of Murine Ventricular Cardiomyocytes.

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_2CDD56FC25F9
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
A Distinct Pool of Nav1.5 Channels at the Lateral Membrane of Murine Ventricular Cardiomyocytes.
Journal
Frontiers in physiology
Author(s)
Rougier J.S., Essers M.C., Gillet L., Guichard S., Sonntag S., Shmerling D., Abriel H.
ISSN
1664-042X (Print)
ISSN-L
1664-042X
Publication state
Published
Issued date
2019
Peer-reviewed
Oui
Volume
10
Pages
834
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
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.
Keywords
dystrophin, electrophysiology, lateral membrane of cardiomyocytes, voltage-gated sodium channel, α1-syntrophin
Pubmed
Web of science
Open Access
Yes
Create date
02/08/2019 16:12
Last modification date
13/12/2019 7:08
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