Beat-to-beat dynamic regulation of intracellular pH in cardiomyocytes.

ABSTRACT: The mammalian heart beats incessantly with rhythmic mechanical activities generating acids that need to be buffered to maintain a stable intracellular pH (pH_i) for normal cardiac function. Even though spatial pH_i non-uniformity in cardiomyocytes has been documented, it remains unknown how pH_i is regulated to match the dynamic cardiac contractions. Here, we demonstrated beat-to-beat intracellular acidification, termed pH_i transients, in synchrony with cardiomyocyte contractions. The pH_i transients are regulated by pacing rate, Cl^-/HCO₃ ^- transporters, pH_i buffering capacity, and β-adrenergic signaling. Mitochondrial electron-transport chain inhibition attenuates the pH_i transients, implicating mitochondrial activity in sculpting the pH_i regulation. The pH_i transients provide dynamic alterations of H⁺ transport required for ATP synthesis, and a decrease in pH_i may 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 pH_i handling in excitable cells.

SUBMITTER: Lyu Y 

PROVIDER: S-EPMC8718820 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature