Cargando…
Phosphorylation of RyR2 Ser‐2814 by CaMKII mediates β1‐adrenergic stress induced Ca(2+)‐leak from the sarcoplasmic reticulum
Adrenergic stimulation, while being the central mechanism of cardiac positive inotropy, is a universally acknowledged inductor of undesirable sarcoplasmic reticulum (SR) Ca(2+) leak. However, the exact mechanisms for this remained unspecified so far. This study shows that Ca(2+)/calmodulin‐dependent...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8487045/ https://www.ncbi.nlm.nih.gov/pubmed/34403217 http://dx.doi.org/10.1002/2211-5463.13274 |
_version_ | 1784577873063968768 |
---|---|
author | Baier, Maria J. Noack, Jannis Seitz, Mark Tilmann Maier, Lars S. Neef, Stefan |
author_facet | Baier, Maria J. Noack, Jannis Seitz, Mark Tilmann Maier, Lars S. Neef, Stefan |
author_sort | Baier, Maria J. |
collection | PubMed |
description | Adrenergic stimulation, while being the central mechanism of cardiac positive inotropy, is a universally acknowledged inductor of undesirable sarcoplasmic reticulum (SR) Ca(2+) leak. However, the exact mechanisms for this remained unspecified so far. This study shows that Ca(2+)/calmodulin‐dependent protein kinase II (CaMKII)‐specific phosphorylation of ryanodine receptor type 2 at Ser‐2814 is the pivotal mechanism by which SR Ca(2+) leak develops downstream of β1‐adrenergic stress by increase of the leak/load relationship. Cardiomyocytes with a Ser‐2814 phosphoresistant mutation (S2814A) were protected from isoproterenol‐induced SR Ca(2+) leak and consequently displayed improved postrest potentiation of systolic Ca(2+) release under adrenergic stress compared to littermate wild‐type cells. |
format | Online Article Text |
id | pubmed-8487045 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-84870452021-10-07 Phosphorylation of RyR2 Ser‐2814 by CaMKII mediates β1‐adrenergic stress induced Ca(2+)‐leak from the sarcoplasmic reticulum Baier, Maria J. Noack, Jannis Seitz, Mark Tilmann Maier, Lars S. Neef, Stefan FEBS Open Bio Research Articles Adrenergic stimulation, while being the central mechanism of cardiac positive inotropy, is a universally acknowledged inductor of undesirable sarcoplasmic reticulum (SR) Ca(2+) leak. However, the exact mechanisms for this remained unspecified so far. This study shows that Ca(2+)/calmodulin‐dependent protein kinase II (CaMKII)‐specific phosphorylation of ryanodine receptor type 2 at Ser‐2814 is the pivotal mechanism by which SR Ca(2+) leak develops downstream of β1‐adrenergic stress by increase of the leak/load relationship. Cardiomyocytes with a Ser‐2814 phosphoresistant mutation (S2814A) were protected from isoproterenol‐induced SR Ca(2+) leak and consequently displayed improved postrest potentiation of systolic Ca(2+) release under adrenergic stress compared to littermate wild‐type cells. John Wiley and Sons Inc. 2021-09-02 /pmc/articles/PMC8487045/ /pubmed/34403217 http://dx.doi.org/10.1002/2211-5463.13274 Text en © 2021 The Authors. FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Baier, Maria J. Noack, Jannis Seitz, Mark Tilmann Maier, Lars S. Neef, Stefan Phosphorylation of RyR2 Ser‐2814 by CaMKII mediates β1‐adrenergic stress induced Ca(2+)‐leak from the sarcoplasmic reticulum |
title | Phosphorylation of RyR2 Ser‐2814 by CaMKII mediates
β1‐adrenergic stress induced Ca(2+)‐leak from the sarcoplasmic reticulum |
title_full | Phosphorylation of RyR2 Ser‐2814 by CaMKII mediates
β1‐adrenergic stress induced Ca(2+)‐leak from the sarcoplasmic reticulum |
title_fullStr | Phosphorylation of RyR2 Ser‐2814 by CaMKII mediates
β1‐adrenergic stress induced Ca(2+)‐leak from the sarcoplasmic reticulum |
title_full_unstemmed | Phosphorylation of RyR2 Ser‐2814 by CaMKII mediates
β1‐adrenergic stress induced Ca(2+)‐leak from the sarcoplasmic reticulum |
title_short | Phosphorylation of RyR2 Ser‐2814 by CaMKII mediates
β1‐adrenergic stress induced Ca(2+)‐leak from the sarcoplasmic reticulum |
title_sort | phosphorylation of ryr2 ser‐2814 by camkii mediates
β1‐adrenergic stress induced ca(2+)‐leak from the sarcoplasmic reticulum |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8487045/ https://www.ncbi.nlm.nih.gov/pubmed/34403217 http://dx.doi.org/10.1002/2211-5463.13274 |
work_keys_str_mv | AT baiermariaj phosphorylationofryr2ser2814bycamkiimediatesb1adrenergicstressinducedca2leakfromthesarcoplasmicreticulum AT noackjannis phosphorylationofryr2ser2814bycamkiimediatesb1adrenergicstressinducedca2leakfromthesarcoplasmicreticulum AT seitzmarktilmann phosphorylationofryr2ser2814bycamkiimediatesb1adrenergicstressinducedca2leakfromthesarcoplasmicreticulum AT maierlarss phosphorylationofryr2ser2814bycamkiimediatesb1adrenergicstressinducedca2leakfromthesarcoplasmicreticulum AT neefstefan phosphorylationofryr2ser2814bycamkiimediatesb1adrenergicstressinducedca2leakfromthesarcoplasmicreticulum |