Compartmentalized β1-adrenergic signalling synchronizes excitation–contraction coupling without modulating individual Ca2+ sparks in healthy and hypertrophied cardiomyocytes

β-adrenergic receptors (βARs) play pivotal roles in regulating cardiac excitation–contraction (E-C) coupling. Global signalling of β₁ARs up-regulates both the influx of Ca²⁺ through sarcolemmal L-type Ca²⁺ channels (LCCs) and the release of Ca²⁺ from the sarcoplasmic reticulum (SR) through the ryanodine receptors (RyRs). However, we recently found that β₂AR stimulation meditates ‘offside compartmentalization’, confining β₁AR signalling into subsarcolemmal nanodomains without reaching SR proteins. In the present study, we aim to investigate the new question, whether and how compartmentalized β₁AR signalling regulates cardiac E-C coupling.