22 - Intracellular pH Regulation

Abstract

This chapter discusses the pH level in the cytoplasm and different compartments of a cell, the variety of mechanisms available to a cell to regulate its pHi and the functional consequences of changes in pHi. Intracellular pH is an important aspect of the intracellular environment. Changes in intracellular pH can potentially affect virtually all cellular processes, including metabolism, membrane potential, cell growth, and movement of substances across the surface membrane, state of polymerization of the cytoskeleton, and ability to contract in muscle cells. Changes of intracellular pH are also often one of the responses of cells to externally applied agents, including growth factors, hormones, and neurotransmitters.. The chapter discusses pH and buffering power and presents the Henderson-Hasselbalch equation, describing the thermodynamic equilibrium that holds for a weak acid in a solution of constant pH. Basically, all of the H+ ions within a cell are buffered by reversible binding to weak acids and bases, resulting in a low free H+ ion activity. Therefore, the activity of free H+ ions within the cytoplasm is usually expressed as cytoplasmic pH (PHi), defined as pH = –log (aH), which is a more convenient scale for molecules at low activities. The chapter discusses several concepts, including intracellular pH, organellar pH, and maintenance of a steady-state pHi, active membrane transport of acids and bases, and cellular functions affected by intracellular pH. Mitochondria, acidic intracellular organelles, and nucleus are discussed under organellar pH. Active membrane transport of acids and bases includes cation-H+ exchangers, HCO3-dependent transporters, H+-ATPases (proton pumps), Na+-organic anion cotransport, chloride-organic anion exchange. The loss of the ability of muscle cells to generate tension (muscle fatigue) has been correlated with a decrease of pHi. It is significant that changes in pH can affect other intracellular signals, such as cellular Ca2+ and cAMP levels, suggesting a complex interaction among cellular signaling systems. Given the importance of pH to so many cellular functions, it is not surprising that cells have elaborated highly regulated mechanisms to control pHi.