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

  • Author(s): 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
  • et al.

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.

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