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

Autor: Yankun Lyu, Phung N. Thai, Lu Ren, Valeriy Timofeyev, Zhong Jian, Seojin Park, Kenneth S. Ginsburg, James Overton, Julie Bossuyt, Donald M. Bers, Ebenezer N. Yamoah, Ye Chen-Izu, Nipavan Chiamvimonvat, Xiao-Dong Zhang
Rok vydání: 2022
Předmět:
Zdroj: iScience
iScience, vol 25, iss 1
iScience, Vol 25, Iss 1, Pp 103624-(2022)
ISSN: 2589-0042
Popis: Summary 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.
Graphical abstract
Highlights • Cardiomyocytes exhibit beat-to-beat cellular acidification, termed “pHi transient.” • pHi transients are coupled to cardiomyocyte contractions and are tightly regulated • Inhibitions of the mitochondrial electron transport chain attenuate pHi transients • pHi transients may reflect a rhythmic metabolic status in cardiomyocytes
Cardiovascular medicine; Molecular biology; Molecular dynamics
Databáze: OpenAIRE
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