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

The mammalian heart beats incessantly with rhythmic mechanical activities generating acids that need to be buffered to maintain a stable intracellular pH (pH) for normal cardiac function. Even though spatial pH non-uniformity in cardiomyocytes has been documented, it remains unknown how pH is regulated to match the dynamic cardiac contractions. Here, we demonstrated beat-to-beat intracellular acidification, termed pH transients, in synchrony with cardiomyocyte contractions. The pH transients are regulated by pacing rate, Cl/HCO transporters, pH buffering capacity, and β-adrenergic signaling. Mitochondrial electron-transport chain inhibition attenuates the pH transients, implicating mitochondrial activity in sculpting the pH regulation. The pH transients provide dynamic alterations of H transport required for ATP synthesis, and a decrease in pH may serve as a negative feedback to cardiac contractions. Current findings dovetail with the prevailing three known dynamic systems, namely electrical, Ca, and mechanical systems, and may reveal broader features of pH handling in excitable cells.