Linscheid, Nora, Logantha, Sunil Jit RJ, Poulsen, Camilla, Zhang, Shanzhuo, Schrolkamp, Maren, Egerod, Kristoffer Lihme, Thompson, Jonatan James, Kitmitto, Ashraf, Galli, Gina, Humphries, Martin J et al (show 5 more authors)
(2019)
Quantitative proteomics and single-nucleus transcriptomics of the sinus node elucidates the foundation of cardiac pacemaking.
Nature Communications, 10 (1).
2889-.
Abstract
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 Ca2+ clock proteins, suggesting that the membrane clock nderpins 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | cardiovascular biology, ion channels, proteomics, RNA sequencing |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 15 Jul 2020 09:21 |
| Last Modified: | 18 Jan 2023 23:45 |
| DOI: | 10.1038/s41467-019-10709-9 |
| Open Access URL: | https://www.nature.com/articles/s41467-019-10709-9 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3094026 |
Dimensions
Dimensions
