Membrane Mechanisms and Intracellular Signalling in Cell Volume Regulation

Abstract

Recent work on selected aspects of the cellular and molecular physiology of cell volume regulation is reviewed. First, the physiological significance of the regulation of cell volume is discussed. Membrane transporters involved in cell volume regulation are reviewed, including volume-sensitive K+ and Cl- channels, K+, Cl- and Na+, K+, 2Cl- cotransporters, and the Na+, H+, Cl-, HCO3-, and K+, H+ exchangers. The role of amino acids, particularly taurine, as cellular osmolytes is discussed. Possible mechanisms by which cells sense their volumes, along with the sensors of these signals, are discussed. The signals are mechanical changes in the membrane and changes in macromolecular crowding. Sensors of these signals include stretch-activated channels, the cytoskeleton, and specific membrane or cytoplasmic enzymes. Mechanisms for transduction of the signal from sensors to transporters are reviewed. These include the Ca(2+)-calmodulin system, phospholipases, polyphosphoinositide metabolism, eicosanoid metabolism, and protein kinases and phosphatases. A detailed model is presented for the swelling-initiated signal transduction pathway in Ehrlich ascites tumor cells. Finally, the coordinated control of volume-regulatory transport processes and changes in the expression of organic osmolyte transporters with long-term adaptation to osmotic stress are reviewed briefly.