Aging Disrupts L-type Ca²⁺ Channel Organization and Function in Pacemaker Cells.

Authors

Oscar Vivas, Matthias Baudot, Roxanne Madden, Wendy L Pinon-Teal, Martina S Hunt, Sabrina Choi, Roya Pournejati, Victor A Flores, L Fernando Santana, Claudia M Moreno

Published in

Circulation research. Jun 19, 2026. Epub Jun 19, 2026.

Abstract

Every heartbeat is initiated by a spontaneous electrical signal generated inside the cardiac pacemaker. This signal depends on the coordinated activity of ion channels, where voltage-gated L-type calcium channels play a central role. All mammals experience a progressive decline in pacemaker rate with age, which in humans can become pathological and drive the need for artificial pacemaker implantation. Yet the mechanisms underlying this age-associated slowdown remain incompletely understood.
We combined patch-clamp electrophysiology, single-channel recording, calcium imaging, immunocytochemistry, and super-resolution microscopy to investigate L-type calcium channel density, organization, and function in sinoatrial node pacemaker cells from young and old mice.
Aging reduced L-type calcium channel density at the plasma membrane, disrupted channel clustering, and decreased open probability, collectively diminishing calcium current density by 50%. Pharmacological enhancement of channel open probability with Bay K 8644 was sufficient to accelerate diastolic depolarization and restore pacemaker rate in old cells to young levels. These channel alterations were paralleled by a decline in caveolin-3 expression. Disrupting caveolae in young cells recapitulated the loss of channel clustering, pointing to caveolae as a structural basis for the age-associated channel alterations.
Aging impairs L-type calcium channel organization and function in cardiac pacemaker cells. This impairment is mediated by an age-associated reduction of caveolae, key membrane microdomains for channel organization. The resulting decline in L-type calcium channel density and activity is an important driver of the age-associated slowdown of the cardiac pacemaker.

PMID:
42318626
Bibliographic data and abstract were imported from PubMed on 19 Jun 2026.

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