The Role of Organic Osmolytes in the Regulation of Mammalian Cell Volume

Abstract

The reasons why mammalian cells require mechanisms enabling them to accurately regulate their volumes (water content), and the ways in which they accomplish this under normal physiological conditions and in response to a wide variety of internal and external stimuli have been comprehensively reviewed over the past two decades (e.g. Hoffmann 1977; Macknight and Leaf 1977; Macknight 1984a; Hoffmann and Simonsen 1989). It is generally agreed that cell membranes are unable to sustain significant osmotic gradients, and that alterations in extracellular osmolality will rapidly be reflected in the osmolality of intracellular fluids, with potentially deleterious changes in cell volume. Cell volumes can also be influenced by factors not immediately related to their external osmotic environment (Macknight 1984b). Thus, for example, cells in the mammalian brain are known to swell under the influence of a variety of non-osmotic stimuli (for references, see Wade et al. 1988). Cells in the kidney, the other organ with which the present chapter is primarily concerned, swell during metabolic blockade (Pine et al. 1979; Linshaw 1980) or ischaemia (Frega et al. 1976): their volumes can also be influenced by the activity of the Na pump and by extracellular oncotic pressure (Linshaw and Stapleton 1978).