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Quantitative proteomics and single-nucleus transcriptomics of the sinus node elucidates the foundation of cardiac pacemaking

The sinus node is a collection of highly specialised cells constituting the heart’s pacemaker. The molecular underpinnings of its pacemaking abilities are debated. Using high-resolution mass spectrometry, we here quantify >7,000 proteins from sinus node and neighbouring atrial muscle. Abundances...

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Autores principales: Linscheid, Nora, Logantha, Sunil Jit R. J., Poulsen, Pi Camilla, Zhang, Shanzhuo, Schrölkamp, Maren, Egerod, Kristoffer Lihme, Thompson, Jonatan James, Kitmitto, Ashraf, Galli, Gina, Humphries, Martin J., Zhang, Henggui, Pers, Tune H., Olsen, Jesper Velgaard, Boyett, Mark, Lundby, Alicia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599035/
https://www.ncbi.nlm.nih.gov/pubmed/31253831
http://dx.doi.org/10.1038/s41467-019-10709-9
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author Linscheid, Nora
Logantha, Sunil Jit R. J.
Poulsen, Pi Camilla
Zhang, Shanzhuo
Schrölkamp, Maren
Egerod, Kristoffer Lihme
Thompson, Jonatan James
Kitmitto, Ashraf
Galli, Gina
Humphries, Martin J.
Zhang, Henggui
Pers, Tune H.
Olsen, Jesper Velgaard
Boyett, Mark
Lundby, Alicia
author_facet Linscheid, Nora
Logantha, Sunil Jit R. J.
Poulsen, Pi Camilla
Zhang, Shanzhuo
Schrölkamp, Maren
Egerod, Kristoffer Lihme
Thompson, Jonatan James
Kitmitto, Ashraf
Galli, Gina
Humphries, Martin J.
Zhang, Henggui
Pers, Tune H.
Olsen, Jesper Velgaard
Boyett, Mark
Lundby, Alicia
author_sort Linscheid, Nora
collection PubMed
description The sinus node is a collection of highly specialised cells constituting the heart’s pacemaker. The molecular underpinnings of its pacemaking abilities are debated. Using high-resolution mass spectrometry, we here quantify >7,000 proteins from sinus node and neighbouring atrial muscle. Abundances of 575 proteins differ between the two tissues. By performing single-nucleus RNA sequencing of sinus node biopsies, we attribute measured protein abundances to specific cell types. The data reveal significant differences in ion channels responsible for the membrane clock, but not in Ca(2+) clock proteins, suggesting that the membrane clock underpins pacemaking. Consistently, incorporation of ion channel expression differences into a biophysically-detailed atrial action potential model result in pacemaking and a sinus node-like action potential. Combining our quantitative proteomics data with computational modeling, we estimate ion channel copy numbers for sinus node myocytes. Our findings provide detailed insights into the unique molecular make-up of the cardiac pacemaker.
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spelling pubmed-65990352019-07-01 Quantitative proteomics and single-nucleus transcriptomics of the sinus node elucidates the foundation of cardiac pacemaking Linscheid, Nora Logantha, Sunil Jit R. J. Poulsen, Pi Camilla Zhang, Shanzhuo Schrölkamp, Maren Egerod, Kristoffer Lihme Thompson, Jonatan James Kitmitto, Ashraf Galli, Gina Humphries, Martin J. Zhang, Henggui Pers, Tune H. Olsen, Jesper Velgaard Boyett, Mark Lundby, Alicia Nat Commun Article The sinus node is a collection of highly specialised cells constituting the heart’s pacemaker. The molecular underpinnings of its pacemaking abilities are debated. Using high-resolution mass spectrometry, we here quantify >7,000 proteins from sinus node and neighbouring atrial muscle. Abundances of 575 proteins differ between the two tissues. By performing single-nucleus RNA sequencing of sinus node biopsies, we attribute measured protein abundances to specific cell types. The data reveal significant differences in ion channels responsible for the membrane clock, but not in Ca(2+) clock proteins, suggesting that the membrane clock underpins pacemaking. Consistently, incorporation of ion channel expression differences into a biophysically-detailed atrial action potential model result in pacemaking and a sinus node-like action potential. Combining our quantitative proteomics data with computational modeling, we estimate ion channel copy numbers for sinus node myocytes. Our findings provide detailed insights into the unique molecular make-up of the cardiac pacemaker. Nature Publishing Group UK 2019-06-28 /pmc/articles/PMC6599035/ /pubmed/31253831 http://dx.doi.org/10.1038/s41467-019-10709-9 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Linscheid, Nora
Logantha, Sunil Jit R. J.
Poulsen, Pi Camilla
Zhang, Shanzhuo
Schrölkamp, Maren
Egerod, Kristoffer Lihme
Thompson, Jonatan James
Kitmitto, Ashraf
Galli, Gina
Humphries, Martin J.
Zhang, Henggui
Pers, Tune H.
Olsen, Jesper Velgaard
Boyett, Mark
Lundby, Alicia
Quantitative proteomics and single-nucleus transcriptomics of the sinus node elucidates the foundation of cardiac pacemaking
title Quantitative proteomics and single-nucleus transcriptomics of the sinus node elucidates the foundation of cardiac pacemaking
title_full Quantitative proteomics and single-nucleus transcriptomics of the sinus node elucidates the foundation of cardiac pacemaking
title_fullStr Quantitative proteomics and single-nucleus transcriptomics of the sinus node elucidates the foundation of cardiac pacemaking
title_full_unstemmed Quantitative proteomics and single-nucleus transcriptomics of the sinus node elucidates the foundation of cardiac pacemaking
title_short Quantitative proteomics and single-nucleus transcriptomics of the sinus node elucidates the foundation of cardiac pacemaking
title_sort quantitative proteomics and single-nucleus transcriptomics of the sinus node elucidates the foundation of cardiac pacemaking
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599035/
https://www.ncbi.nlm.nih.gov/pubmed/31253831
http://dx.doi.org/10.1038/s41467-019-10709-9
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