- Lyu, Yankun;
- Thai, Phung N;
- Ren, Lu;
- Timofeyev, Valeriy;
- Jian, Zhong;
- Park, Seojin;
- Ginsburg, Kenneth S;
- Overton, James;
- Bossuyt, Julie;
- Bers, Donald M;
- Yamoah, Ebenezer N;
- Chen-Izu, Ye;
- Chiamvimonvat, Nipavan;
- Zhang, Xiao-Dong
The 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 pHi non-uniformity in cardiomyocytes has been documented, it remains unknown how pHi is regulated to match the dynamic cardiac contractions. Here, we demonstrated beat-to-beat intracellular acidification, termed pHi transients, in synchrony with cardiomyocyte contractions. The pHi transients are regulated by pacing rate, Cl-/HCO3 - transporters, pHi buffering capacity, and β-adrenergic signaling. Mitochondrial electron-transport chain inhibition attenuates the pHi transients, implicating mitochondrial activity in sculpting the pHi regulation. The pHi transients provide dynamic alterations of H+ transport required for ATP synthesis, and a decrease in pHi 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 pHi handling in excitable cells.