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(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(−)/HCO(3)(-) 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, Ca(2+), and mechanical systems, and may reveal broader features of pH(i) handling in excitable cells.