Swelling-activated organic osmolyte channels.

Abstract

Most cells have in their cytosols substantial (i.e., umillimolar) concentrations of low molecular weight organic solutes which, together, make a significant contribution to the total intracellular osmolality and which are known collectively as ‘organic osmolytes’. The solutes fulfilling this role fall, in most cases, into one of three different classes: amino acids (e.g., the a-amino acids alanine and proline, and the b-amino acids taurine and b-alanine), polyols (e.g., sorbitol and myo-inositol), and methylamines (e.g., betaine and glycerophosphoryl choline). Such compounds are either synthesized within the cell or taken up from the extracellular medium via accumulative (‘active’) transport systems. In contrast to inorganic ions which, at high concentrations, destabilize protein structure, these organic solutes exert a stabilizing influence on intracellular proteins and, for this reason, are termed ‘compatible solutes’ (Yancey, 1994). The identity and intracellular concentrations of the major organic osmolytes vary between cell-types, as well as with the conditions to which the cells are exposed. Intracellular levels of these compounds increase markedly in response to cell shrinkage. Conversely, a common phenomenon that has been demonstrated for a wide range of cells is that such compounds are released in response to an acute increase in the cell volume, as occurs, for example, following a sudden decrease in the extracellular osmolality. Their loss from the cell is accompanied by a net efflux of water and this process thereby serves as part of the cell’s volume-regulatory response. From studies of swelling-activated organic osmolyte transport in cells from a diverse range of organisms it has emerged that the transport pathways involved share a number of functional characteristics. There is increasing evidence that these pathways are, in many cases and perhaps in general, channels that have a significant permeability to a wide variety of both charged and uncharged solutes. The purpose of this review is to summarize what is currently known about these pathways in eukaryotic cells. The focus is on the properties of the pathways themselves. The mechanisms underlying their volume-sensitivity and the regulatory processes involved in their activation are not considered in any detail. Current ideas concerning the functional and molecular characteristics of the pathways are discussed. However, before turning to these issues it is relevant to consider the relative contribution that these pathways make to the process of ‘regulatory volume decrease’ (RVD) in different cell and tissue types.