Last update:
13-Jan-2026

The ability to regulate cell volume is vital for maintaining cellular homeostasis and performing key functions, including cell proliferation, transepithelial ion transport, cell migration, and apoptosis, among others. Several transmembrane proteins, such as channels, transporters, and ion pumps, play a significant role in this regulatory process. Contributor to the cell volume regulation is the hydraulic conductivity of the plasma membrane, which is largely determined by the availability of aquaporins. Under conditions of osmotic imbalance between extracellular and intracellular compartments, the cell employs mechanisms of regulatory volume increase (RVI) in hypertonic extracellular environments and regulatory volume decrease (RVD) in hypotonic conditions. The proper function of these mechanisms constitutes a homeostatic process of critical importance for the physiology of all cells, and it is extensively analyzed in this review. To facilitate these mechanisms, the involvement of transcription factors is necessary, as they regulate the expression of osmoprotective genes. Finally, special attention is given to the principal and intercalated cells of the renal tubules, which, given the osmolarity gradient described in the renal medulla that can reach up to 1,200 mOsm/ kg, are the cells of the body that possess the most robust mechanisms for cell volume regulation.

Key words: Aquaporins, Cell volume regulation, Ion channels, Ion transporters, Osmolarity.