Swelling detection for volume regulation in the primitive eukaryote Giardia intestinalis: a common feature of volume detection in present-day eukaryotes.

It is increasingly evident that cell swelling is associated with the triggering of many biological processes, including progression of the cell cycle, hormonal response, and gene expression. However, the mechanism by which cell swelling is initially sensed and converted into intracellular signals is still ill-defined. We report here an early event in the detection of cell swelling and initiation of the volume regulatory response in Giardia intestinalis, an ancient representative of the eukaryotic kingdom. Giardial cell swelling, irrespective of the extent, was sensed at a cell volume of 1.06 x isosmotic volume (the threshold volume), at which the transition of the volume regulatory transport system from the 'resting' to the 'open' state occurred. Irreversible modification by p-chloromercuribenzoate (pCMB) and N-ethylmaleimide (NEM) of reduced thiols affected the threshold volume, but in opposing manners: pCMB increased the threshold volume to 1.14 x and NEM decreased to 0.85 x isosmotic volume. The simple modification of the threshold volume by NEM caused a drastic reduction of giardial cell volume under isosmotic conditions, with a process strikingly similar to the opening of mitochondrial permeability transition pore, a causative event in stress-induced programmed cell death. Substantial evidence supports the hypothesis that modulation of the membrane thiol moieties at the threshold volume, causing the 'all-or-nothing' type of swelling detection, represents the event linking cell swelling to the second messenger systems for volume regulation in present eukaryotes. Pathophysiological implications of alteration of the threshold volume are discussed.