Aging Alters the Formation and Functionality of Signaling Microdomains Between L-type Calcium Channels and β2-Adrenergic Receptors in Cardiac Pacemaker Cells

• DOI: 10.3389/fphys.2022.805909
• Publication Date: 2022-04-20T06:04:17Z
• Authors: Sabrina Choi; Oscar Vivas; Matthias Baudot; Claudia M. Moreno
• Keywords: Calcium Signaling; Pacemaker potential; L-type calcium channel; Lipid microdomain; Cardiac pacemaker

Heart rate is accelerated to match physiological demands through the action of noradrenaline on cardiac pacemaker. Noradrenaline released from sympathetic terminals and activates β1-and β2-adrenergic receptors (ΑRs) located at plasma membrane pacemaker cells. L-type calcium channels are one main downstream targets potentiated by activation β-ARs. For this signaling occur, need be in close proximity β-ARs inside caveolae. Although it known that aging causes a slowdown reduction response cells noradrenaline, there lack in-depth mechanistic insights into these age-associated changes. Here, we show affects formation function adrenergic microdomains By evaluating β1 β2 components regulation current, does not alter mediated β1-ARs but drastically impairs β2-ARs. We studied integrity formed between combining high-resolution microscopy ligation assays. consistent with electrophysiological data, decreases physical association β2-ARs channels. Interestingly, associated decrease scaffolding protein AKAP150. Old also have caveolae density caveolin-3. Together age-dependent alterations caveolar nano-organization result reduced sensitivity modulation. Our results highlight importance maintaining chronotropic modulation heart pinpoint direct impact has their function.