Beat-locked ATP microdomains in the sinoatrial node map a Ca²⁺-timed energetic hierarchy and regional pacemaker roles.

ABSTRACT: Pacemaker myocytes of the sinoatrial (SA) node initiate each heartbeat through coupled voltage and Ca²⁺ oscillators, but whether ATP supply is regulated on a beat-by-beat schedule in these cells has been unclear. Using genetically encoded sensors targeted to the cytosol and mitochondria, we tracked beat-resolved ATP dynamics in intact mouse SA node and isolated myocytes. Cytosolic ATP rose transiently with each Ca²⁺ transient and segregated into high- and low-gain phenotypes defined by the Ca²⁺-ATP coupling slope. Mitochondrial ATP flux adopted two stereotyped waveforms-Mode-1 "gains" and Mode-2 "dips." Within Mode-1 cells, ATP gains mirrored the cytosolic high/low-gain dichotomy; Mode-2 dips scaled linearly with Ca²⁺ load and predominated in slo

SUBMITTER: Munoz MF 

PROVIDER: S-EPMC12393423 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature