- 著者
-
Sandoval Moises
Burgos Johanna
Sepulveda Francisco V.
Cid L. Pablo
- 出版者
- 公益社団法人 日本薬学会
- 雑誌
- Biological & Pharmaceutical Bulletin (ISSN:09186158)
- 巻号頁・発行日
- vol.34, no.6, pp.803-809, 2011
- 被引用文献数
-
10
The importance of intracellular pH (pH<sub>i</sub>) 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 (pH<sub>o</sub>), 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 pH<sub>o</sub>-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 pH<sub>o</sub> in confined spaces of native epithelial tissue.