Centro de Estudios Científicos (CECS), Valdivia, Chile.
Biol Pharm Bull. 2011;34(6):803-9. doi: 10.1248/bpb.34.803.
The importance of intracellular pH (pH(i)) in the regulation of diverse cellular activities ranging from cell proliferation and differentiation to cell cycle, migration and apoptosis has long been recognised. More recently, extracellular pH (pH₀), in particular that of relatively inaccessible compartments or domains that occur between cells in tissues, has begun to be acknowledged as a relevant signal in cell regulation. This should not be surprising given the abundant reports highlighting the pH₀-dependence of the activity of membrane proteins facing the extracellular space such as receptors, transporters, ion channels and enzymes. Changes in pH affect the ionisation state of proteins through the effect on their titratable groups. There are proteins, however, which respond to pH shifts with conformational changes that are crucial for catalysis or transport activity. In such cases protons act as signalling molecules capable of eliciting fast and localised responses. We provide examples of ion channels that appear fastidiously designed to respond to extracellular pH in a manner that suggests specific functions in transporting epithelia. We shall also present ideas as to how these channels participate in complex transepithelial transport processes and provide preliminary experiments illustrating a new way to gauge pH₀ in confined spaces of native epithelial tissue.
细胞内 pH（pH(i)）在调节多种细胞活动中的重要性早已被认识，这些活动包括细胞增殖和分化、细胞周期、迁移和凋亡。最近，细胞外 pH（pH₀），特别是细胞间相对难以接近的细胞外空间或区域的 pH₀，已开始被认为是细胞调节中的一个相关信号。鉴于大量报道强调了面向细胞外空间的膜蛋白（如受体、转运蛋白、离子通道和酶）的活性对 pH₀的依赖性，这并不奇怪。pH 的变化通过影响其可滴定基团来影响蛋白质的离子化状态。然而，有些蛋白质对 pH 变化的响应是通过构象变化来实现的，这对于催化或运输活性至关重要。在这种情况下，质子可以作为信号分子，能够引发快速和局部的响应。我们提供了一些离子通道的例子，这些通道似乎经过精心设计，可以以一种暗示在运输上皮组织中具有特定功能的方式对细胞外 pH 做出响应。我们还将提出这些通道如何参与复杂的跨上皮运输过程的想法，并提供初步实验，说明一种新的方法来测量天然上皮组织中封闭空间中的 pH₀。
