[The importance of intracellular pH in the regulation of cell function]

Cell life is possible only if intracellular pH (pHi) oscillations are kept within a very narrow range. Measurement of pHi is therefore a very important parameter when examining cell and organ functions. Several methods have been used to monitor pHi; these include fluorescent dyes and pH sensitive electrodes. In addition, many instruments have been applied to the detection of pHi in living organs even at the level of single cells: NMR and confocal microscopy are just an example. Transport proteins located on the cell membrane and intracellular vesicles are responsible for maintaining the correct pHi. In renal tubular cells these include the sodium hydrogen exchanger (NHE), the sodium-dependent and independent chloride-bicarbonate exchanger (Cl--HCO3-), the sodium bicarbonate co-transport (Na+-HCO3-), the ATP-coupled proton pump (H+-ATPasi) and the ATP-dependent proton-potassium pump (H+-K+-ATPasi). All these carriers have been cloned and it is now clear that there are several isoforms with specific properties. The function of these proteins is closely linked to several hormone blood levels, systemic acid-base status, protein diet content as well as other factors. In addition, these carriers are not homogeneously distributed along the nephron and are sensitive to specific stimuli like interstitial osmolality and luminal fluid flow rate. Finally, it has been recently demonstrated that the pHi may be involved in numerous aspects of cell function, such as metabolism, apoptosis, malignancy and it is implicated in the pathogenesis of particular forms of renal stones (Dent's disease).