Intracellular pH (pHi) is the measure of the acidity or basicity (i.e., pH) of intracellular fluid. The pHi plays a critical role in membrane transport and other intracellular processes. In an environment with the improper pHi, biological cells may have compromised function. Therefore, pHi is closely regulated in order to ensure proper cellular function, controlled cell growth, and normal cellular processes. The mechanisms that regulate pHi are usually considered to be plasma membrane transporters of which two main types exist — those that are dependent and those that are independent of the concentration of bicarbonate (). Physiologically normal intracellular pH is most commonly between 7.0 and 7.4, though there is variability between tissues (e.g., mammalian skeletal muscle tends to have a pHi of 6.8–7.1). There is also pH variation across different organelles, which can span from around 4.5 to 8.0. pHi can be measured in a number of different ways. Homeostasis Intracellular pH is typically lower than extracellular pH due to lower concentrations of HCO3−. A rise of extracellular (e.g., serum) partial pressure of carbon dioxide (pCO2) above 45 mmHg leads to formation of carbonic acid, which causes a decrease of pHi as it dissociates: H2O + CO2 H2CO3 H+ + HCO3– Since biological cells contain fluid that can act as a buffer, pHi can be maintained fairly well within a certain range. Cells adjust their pHi accordingly upon an increase in acidity or basicity, usually with the help of CO2 or HCO3– sensors present in the membrane of the cell. These sensors can permit H+ to pass through the cell membrane accordingly, allowing for pHi to be interrelated with extracellular pH in this respect. Major intracellular buffer systems include those involving proteins or phosphates. Since the proteins have acidic and basic regions, they can serve as both proton donors or acceptors in order to maintain a relatively stable intracellular pH. In the case of a phosphate buffer, substantial quantities of weak acid and conjugate weak base (H2PO4– and HPO42–) can accept or donate protons accordingly in order to conserve intracellular pH: OH– + H2PO4– H2O + HPO42– H+ + HPO42– H2PO4– In organelles The pH within a particular organelle is tailored for its specific function. For example, lysosomes have a relatively low pH of 4.5. Additionally, fluorescence microscopy techniques have indicated that phagocytes also have a relatively low internal pH. Since these are both degradative organelles that engulf and