Functional Significance of Cell Volume Regulatory Mechanisms

Abstract

To survive, cells have to avoid excessive alterations of cell volume that jeopardize structural integrity and constancy of intracellular milieu. The function of cellular proteins seems specifically sensitive to dilution and concentration, determining the extent of macromolecular crowding. Even at constant extracellular osmolarity, volume constancy of any mammalian cell is permanently challenged by transport of osmotically active substances across the cell membrane and formation or disappearance of cellular osmolarity by metabolism. Thus cell volume constancy requires the continued operation of cell volume regulatory mechanisms, including ion transport across the cell membrane as well as accumulation or disposal of organic osmolytes and metabolites. The various cell volume regulatory mechanisms are triggered by a multitude of intracellular signaling events including alterations of cell membrane potential and of intracellular ion composition, various second messenger cascades, phosphorylation of diverse target proteins, and altered gene expression. Hormones and mediators have been shown to exploit the volume regulatory machinery to exert their effects. Thus cell volume may be considered a second message in the transmission of hormonal signals. Accordingly, alterations of cell volume and volume regulatory mechanisms participate in a wide variety of cellular functions including epithelial transport, metabolism, excitation, hormone release, migration, cell proliferation, and cell death.

Intracellular acidification by inhibition of the Na+/H+-exchanger leads to caspase-independent death of cerebellar granule neurons resembling paraptosis

“…23 We report here for the first time that potassium withdrawal leads to acidification in cerebellar granule neurons that is not due to changes in osmolarity (Figure 1d). However, alkalization of the medium did not block potassium withdrawalinduced apoptosis (Figure 3).…”

“…As potassium is involved in many physiological processes of the cell, for example, the regulation of the pH i , 23 there possibly exists a calcium-independent mechanism in cerebellar granule neurons associated with the redistribution of potassium after its withdrawal. Therefore, we investigated the changes in pH i occurring between 15 and 240 min after potassium deprivation (Figure 1c, d).…”

Mild dehydration: a risk factor of broncho-pulmonary disorders?

“…There is increasing evidence that fluid intake and renal and extrarenal fluid losses vary between individuals, and that hydration status is not uniform in the population as well. Recent research indicates that dehydration may impair metabolism on a cellular level (Häussinger et al, 1993;Lang et al, 1998;Kleiner, 1999).…”

Effects of changes in water compartments on physiology and metabolism

“…The cell swelling theory was introduced by D Häussinger in the 1990s (Häussinger et al, 1994;Häussinger & Schliess, 1995;Lang et al, 1998). This new concept in physiology argues that cellular volume is a key signal for the metabolic orientation of cell metabolism, namely cellular swelling leads to anabolism whereas cellular shrinkage promotes catabolism.…”

“…This is true for hepatocytes, muscle cells, mitochondria, and also bone and breast cells (Lang et al, 1998). There is little doubt that some cells can face large osmolarity changes (for example, hepatocytes following portal delivery of substrates by the gut, kidney cells along the Henle's tubule).…”