Quantitative proteomics of mouse heart tissue revealed significant differences in membrane clock ion channels, but not Ca2+ clock proteins, between the sinus node and atrial muscle, suggesting the membrane clock underpins cardiac pacemaking.
Multi-omics analysis of the sinus node suggests that the membrane clock, rather than the calcium clock, is the primary driver of cardiac pacemaking.
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 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.
Linscheid et al. (2019) studied Healthy (animal model) (n=30). Sinus node tissue vs. Right atrial muscle was evaluated on Differential protein expression between sinus node and atrial muscle. Quantitative proteomics of mouse heart tissue revealed significant differences in membrane clock ion channels, but not Ca2+ clock proteins, between the sinus node and atrial muscle, suggesting the membrane clock underpins cardiac pacemaking.