Beat-to-beat dynamic regulation of intracellular pH in cardiomyocytes
Yankun Lyu1, Phung N Thai1, Lu Ren1
1Department of Internal Medicine, University of California, Davis, Davis, CA 95616, USA.
Insights
Cardiac cells exhibit beat-to-beat intracellular pH (pHi) transients synchronized with contractions. These pHi changes are regulated by various factors and may influence ATP synthesis and cardiac function.
Area of Science:
- Cardiology
- Cell Physiology
- Biochemistry
Background:
- Mammalian heart function relies on stable intracellular pH (pHi) despite acid production during contractions.
- Previous research noted spatial pHi non-uniformity but lacked understanding of its dynamic regulation during cardiac cycles.
Purpose of the Study:
- To investigate the beat-to-beat regulation of intracellular pH (pHi) in cardiomyocytes during contractions.
- To identify factors influencing these dynamic pHi changes and their functional implications.
Main Methods:
- Utilized techniques to measure intracellular pH (pHi) transients in cardiomyocytes.
- Investigated the effects of pacing rate, ion transporters, buffering capacity, and signaling pathways on pHi transients.
- Examined the role of mitochondrial activity via electron-transport chain inhibition.
Main Results:
- Demonstrated synchronized beat-to-beat intracellular acidification (pHi transients) with cardiomyocyte contractions.
- Identified pacing rate, Cl-/HCO3 - transporters, buffering capacity, and β-adrenergic signaling as key regulators.
- Showed that mitochondrial electron-transport chain inhibition attenuates pHi transients, highlighting mitochondrial involvement.
Conclusions:
- pHi transients are a dynamic feature of cardiomyocyte function, coupled to contractions.
- These transients play a role in regulating H+ transport for ATP synthesis and may act as negative feedback on contractions.
- Findings add a new dimension to the understanding of dynamic systems in excitable cells, including electrical, Ca2+, and mechanical systems.
Abstract:
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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