English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Axial tubule junctions control rapid calcium signaling in atria.

Brandenburg, S., Kohl, T., Williams, G. S. B., Gusev, K., Wagner, E., Rog-Zielinska, E. A., et al. (2016). Axial tubule junctions control rapid calcium signaling in atria. Journal of Clinical Investigation, 126(10), 3999-4015. doi:10.1172/JCI88241.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002B-AAD8-3 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002C-9250-7
Genre: Journal Article

Files

show Files
hide Files
:
2354387.pdf (Publisher version), 4MB
 
File Permalink:
-
Name:
2354387.pdf
Description:
-
Visibility:
Restricted (Max Planck Institute for Biophysical Chemistry (Karl Friedrich Bonhoeffer Institute), Göttingen; )
MIME-Type / Checksum:
application/pdf
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-

Locators

show
hide
Locator:
https://www.jci.org/articles/view/88241 (Publisher version)
Description:
-

Creators

show
hide
 Creators:
Brandenburg, S., Author
Kohl, T., Author
Williams, G. S. B., Author
Gusev, K., Author
Wagner, E., Author
Rog-Zielinska, ED. A., Author
Hebisch, E.1, Author              
Dura, M., Author
Didie, M., Author
Gotthardt, M., Author
Nikolaev, V. O., Author
Hasenfuss, G., Author
Kohl, P., Author
Ward, C. W., Author
Lederer, W. J., Author
Lehnart, S. E., Author
Affiliations:
1Department of NanoBiophotonics, MPI for Biophysical Chemistry, Max Planck Society, ou_578627              

Content

show
hide
Free keywords: -
 Abstract: The canonical atrial myocyte (AM) is characterized by sparse transverse tubule (TT) invaginations and slow intracellular Ca2+ propagation but exhibits rapid contractile activation that is susceptible to loss of function during hypertrophic remodeling. Here, we have identified a membrane structure and Ca2+-signaling complex that may enhance the speed of atrial contraction independently of phospholamban regulation. This axial couplon was observed in human and mouse atria and is composed of voluminous axial tubules (ATs) with extensive junctions to the sarcoplasmic reticulum (SR) that include ryanodine receptor 2 (RyR2) clusters. In mouse AM, AT structures triggered Ca2+ release from the SR approximately 2 times faster at the AM center than at the surface. Rapid Ca2+ release correlated with colocalization of highly phosphorylated RyR2 clusters at AT-SR junctions and earlier, more rapid shortening of central sarcomeres. In contrast, mice expressing phosphorylation-incompetent RyR2 displayed depressed AM sarcomere shortening and reduced in vivo atrial contractile function. Moreover, left atrial hypertrophy led to AT proliferation, with a marked increase in the highly phosphorylated RyR2-pS2808 cluster fraction, thereby maintaining cytosolic Ca2+ signaling despite decreases in RyR2 cluster density and RyR2 protein expression. AT couplon "super-hubs" thus underlie faster excitation-contraction coupling in health as well as hypertrophic compensatory adaptation and represent a structural and metabolic mechanism that may contribute to contractile dysfunction and arrhythmias.

Details

show
hide
Language(s): eng - English
 Dates: 2016-09-192016-10-03
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1172/JCI88241
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Journal of Clinical Investigation
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 126 (10) Sequence Number: - Start / End Page: 3999 - 4015 Identifier: -