摘要:SummaryThe mammalian heart beats incessantly with rhythmic mechanical activities generating acids that need to be buffered to maintain a stable intracellular pH (pHi) for normal cardiac function. Even though spatial pHinon-uniformity in cardiomyocytes has been documented, it remains unknown how pHiis regulated to match the dynamic cardiac contractions. Here, we demonstrated beat-to-beat intracellular acidification, termed pHitransients, in synchrony with cardiomyocyte contractions. The pHitransients are regulated by pacing rate, Cl−/HCO3-transporters, pHibuffering capacity, and β-adrenergic signaling. Mitochondrial electron-transport chain inhibition attenuates the pHitransients, implicating mitochondrial activity in sculpting the pHiregulation. The pHitransients provide dynamic alterations of H+transport required for ATP synthesis, and a decrease in pHimay serve as a negative feedback to cardiac contractions. Current findings dovetail with the prevailing three known dynamic systems, namely electrical, Ca2+, and mechanical systems, and may reveal broader features of pHihandling in excitable cells.Graphical abstractDisplay OmittedHighlights•Cardiomyocytes exhibit beat-to-beat cellular acidification, termed “pHitransient.”•pHitransients are coupled to cardiomyocyte contractions and are tightly regulated•Inhibitions of the mitochondrial electron transport chain attenuate pHitransients•pHitransients may reflect a rhythmic metabolic status in cardiomyocytesCardiovascular medicine; Molecular biology; Molecular dynamics