Studio Tecnico Ing. Laura Molinari, 37138 Verona, Italy.
Member of IEEE, Piscataway, NJ 08855, U.S.A.
Biochem J. 2021 Feb 26;478(4):895-910. doi: 10.1042/BCJ20200971.
Thirty-six years after the publication of the important article by Busa and Nuccitelli on the variability of intracellular pH (pHi) and the interdependence of pHi and intracellular Ca2+ concentration ([Ca2+]i), little research has been carried out on pHi and calcium signaling. Moreover, the results appear to be contradictory. Some authors claim that the increase in [Ca2+]i is due to a reduction in pHi, others that it is caused by an increase in pHi. The reasons for these conflicting results have not yet been discussed and clarified in an exhaustive manner. The idea that variations in pHi are insignificant, because cellular buffers quickly stabilize the pHi, may be a limiting and fundamentally wrong concept. In fact, it has been shown that protons can move and react in the cell before they are neutralized. Variations in pHi have a remarkable impact on [Ca2+]i and hence on some of the basic biochemical mechanisms of calcium signaling. This paper focuses on the possible triggering role of protons during their short cellular cycle and it suggests a new hypothesis for an IP3 proton dependent mechanism of action.
在 Busa 和 Nuccitelli 发表关于细胞内 pH 值 (pHi) 变异性和 pHi 与细胞内 Ca2+浓度 ([Ca2+]i) 相互依赖性的重要文章 36 年后,对 pHi 和钙信号转导的研究甚少。此外,结果似乎相互矛盾。一些作者声称 [Ca2+]i 的增加是由于 pHi 降低引起的,而另一些作者则认为是由于 pHi 升高引起的。这些相互矛盾的结果的原因尚未以详尽的方式进行讨论和澄清。由于细胞缓冲液可以快速稳定 pHi,因此认为 pHi 变化不重要的观点可能是一个限制和根本错误的概念。事实上,已经表明质子在被中和之前可以在细胞内移动和反应。pHi 的变化对 [Ca2+]i 有显著影响,因此对钙信号转导的一些基本生化机制有显著影响。本文重点关注质子在其短细胞周期内可能的触发作用,并提出了一种新的关于 IP3 质子依赖作用机制的假设。