β2‐adrenergic stimulation potentiates spontaneous calcium release by increasing signal mass and co‐activation of ryanodine receptor clusters

• Published in: Acta Physiologica 2022-04, Vol.234 (4), p.e13736-n/a
• Main Authors: Nolla‐Colomer, Carme, Casabella‐Ramon, Sergi, Jimenez‐Sabado, Veronica, Vallmitjana, Alexander, Tarifa, Carmen, Herraiz‐Martínez, Adela, Llach, Anna, Tauron, Manel, Montiel, Jose, Cinca, Juan, Chen, S. R. Wayne, Benitez, Raul, Hove‐Madsen, Leif
• Format: Article
• Language: English
• Subjects: Adrenergic Agents; Animals; Atrial Fibrillation - metabolism; Calcium - metabolism; Calcium imaging; Calcium Signaling; Calcium signalling; calcium spark; Cardiac arrhythmia; cardiac myocyte; Cardiomyocytes; confocal imaging; Fibrillation; Firing rate; Green fluorescent protein; Humans; Labeling; Mice; Myocytes; Myocytes, Cardiac - metabolism; Phosphorylation; Receptor density; ryanodine receptor; Ryanodine Receptor Calcium Release Channel - metabolism; Ryanodine receptors; sarcoplasmic reticulum; Sarcoplasmic Reticulum - metabolism; β‐adrenergic
• ISSN: 1748-1708; 1748-1716
• DOI: 10.1111/apha.13736

Aims It is unknown how β‐adrenergic stimulation affects calcium dynamics in individual RyR2 clusters and leads to the induction of spontaneous calcium waves. To address this, we analysed spontaneous calcium release events in green fluorescent protein (GFP)‐tagged RyR2 clusters. Methods Cardiomyocytes from mice with GFP‐tagged RyR2 or human right atrial tissue were subjected to immunofluorescent labelling or confocal calcium imaging. Results Spontaneous calcium release from single RyR2 clusters induced 91.4% ± 2.0% of all calcium sparks while 8.0% ± 1.6% were caused by release from two neighbouring clusters. Sparks with two RyR2 clusters had 40% bigger amplitude, were 26% wider, and lasted 35% longer at half maximum. Consequently, the spark mass was larger in two‐ than one‐cluster sparks with a median and interquartile range for the cumulative distribution of 15.7 ± 20.1 vs 7.6 ± 5.7 a.u. (P