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
Department of Internal Medicine, University of California, Davis, Davis, CA 95616, USA.
Department of Pharmacology, University of California, Davis, Davis, CA 95616, USA.
iScience. 2021 Dec 13;25(1):103624. doi: 10.1016/j.isci.2021.103624. eCollection 2022 Jan 21.
The mammalian heart beats incessantly with rhythmic mechanical activities generating acids that need to be buffered to maintain a stable intracellular pH (pH) for normal cardiac function. Even though spatial pH non-uniformity in cardiomyocytes has been documented, it remains unknown how pH is regulated to match the dynamic cardiac contractions. Here, we demonstrated beat-to-beat intracellular acidification, termed pH transients, in synchrony with cardiomyocyte contractions. The pH transients are regulated by pacing rate, Cl/HCO transporters, pH buffering capacity, and β-adrenergic signaling. Mitochondrial electron-transport chain inhibition attenuates the pH transients, implicating mitochondrial activity in sculpting the pH regulation. The pH transients provide dynamic alterations of H transport required for ATP synthesis, and a decrease in pH may serve as a negative feedback to cardiac contractions. Current findings dovetail with the prevailing three known dynamic systems, namely electrical, Ca, and mechanical systems, and may reveal broader features of pH handling in excitable cells.
哺乳动物的心脏持续跳动，其有节律的机械活动会产生酸性物质，这些酸性物质需要被缓冲，以维持稳定的细胞内pH值（pH），从而保证心脏的正常功能。尽管已经有文献记载心肌细胞内存在空间pH值不均匀的情况，但pH值是如何被调节以匹配心脏动态收缩的仍不清楚。在这里，我们证明了与心肌细胞收缩同步的逐搏细胞内酸化现象，即pH值瞬变。pH值瞬变受起搏频率、Cl/HCO转运体、pH缓冲能力和β-肾上腺素能信号传导的调节。线粒体电子传递链抑制会减弱pH值瞬变，这表明线粒体活动参与了pH值调节的塑造过程。pH值瞬变提供了ATP合成所需的H转运的动态变化，pH值降低可能作为对心脏收缩的负反馈。目前的研究结果与现有的三个已知动态系统，即电、钙和机械系统相吻合，可能揭示了可兴奋细胞中pH值处理的更广泛特征。
