Nanoscale visualization of functional adhesion/excitability nodes at the intercalated disc

Alejandra Leo-Macias, Esperanza Agullo-Pascual, Jose L. Sanchez-Alonso, Sarah Keegan, Xianming Lin, Tatiana Arcos, Feng-Xia-Liang, Yuri E. Korchev, Julia Gorelik (), David Fenyö (), Eli Rothenberg and Mario Delmar ()
Additional contact information
Alejandra Leo-Macias: New York University School of Medicine (NYU-SoM)
Esperanza Agullo-Pascual: New York University School of Medicine (NYU-SoM)
Jose L. Sanchez-Alonso: Imperial College, National Heart and Lung Institute, Imperial Center for Translational and Experimental Medicine, Hammersmith Campus
Sarah Keegan: Center for Health Informatics and Bioinformatics, NYU-SoM
Xianming Lin: New York University School of Medicine (NYU-SoM)
Tatiana Arcos: New York University School of Medicine (NYU-SoM)
Feng-Xia-Liang: Microscopy Core, NYU-SoM
Yuri E. Korchev: Imperial College, Hammersmith Campus
Julia Gorelik: Imperial College, National Heart and Lung Institute, Imperial Center for Translational and Experimental Medicine, Hammersmith Campus
David Fenyö: Center for Health Informatics and Bioinformatics, NYU-SoM
Eli Rothenberg: NYU-SoM
Mario Delmar: New York University School of Medicine (NYU-SoM)

Nature Communications, 2016, vol. 7, issue 1, 1-12

Abstract: Abstract Intercellular adhesion and electrical excitability are considered separate cellular properties. Studies of myelinated fibres, however, show that voltage-gated sodium channels (VGSCs) aggregate with cell adhesion molecules at discrete subcellular locations, such as the nodes of Ranvier. Demonstration of similar macromolecular organization in cardiac muscle is missing. Here we combine nanoscale-imaging (single-molecule localization microscopy; electron microscopy; and ‘angle view’ scanning patch clamp) with mathematical simulations to demonstrate distinct hubs at the cardiac intercalated disc, populated by clusters of the adhesion molecule N-cadherin and the VGSC NaV1.5. We show that the N-cadherin-NaV1.5 association is not random, that NaV1.5 molecules in these clusters are major contributors to cardiac sodium current, and that loss of NaV1.5 expression reduces intercellular adhesion strength. We speculate that adhesion/excitability nodes are key sites for crosstalk of the contractile and electrical molecular apparatus and may represent the structural substrate of cardiomyopathies in patients with mutations in molecules of the VGSC complex.

Date: 2016
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms10342 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10342

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms10342

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().